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Research Resources222
  
DPPDiabetes; ObesityHealth Disparities; Interventional Trial; Racial Disparitieshttps://www.niddkrepository.org/studies/dpp/http://www.bsc.gwu.edu/dpp/index.htmlvdocLinder, Barbara (NIH/NIDDK) [E]NoNoNo4/24/2014 11:46 AM
The DPP showed that lifestyle change or metformin delay the development of type 2 diabetes. The DPPOS is a long-term follow-up study of the DPP participants.
Research Resources223
  
DPPOSDiabetesEpidemiology; Health Disparities; Interventional Trial; Racial Disparitieshttps://www.niddkrepository.org/studies/dppos/http://www.bsc.gwu.edu/dpp/protocol.htmlvdocLinder, Barbara (NIH/NIDDK) [E]NoNoNo4/24/2014 11:44 AM
The Diabetes Prevention Program Outcomes Study is studying the long term effect of diet and exercise and the diabetes medication, metformin, on the delay of type 2 diabetes in participants of the Diabetes Prevention Program (DPP).
Research Resources253
  
dkNETDiabetes; Digestive Disease; Endocrine Disease and Metabolic Disease; Hematologic Disease; Liver Disease; Nutrition; Obesity; Pancreatic Disease; Urologic DiseaseBiomarkers; Biosamples; DNA; Tissues; Datasets; Model Systems; Animal Models; Cell Lines; Zebrafish; Protocols and Methods; Histology; Morphology; Phenotyping; Reagents; Antibodies; Primers; VectorsCell Biology and Physiology; Developmental Biology; Fibrosis; Pathobiology; Stem Cell Biology; Clinical Research; Ancillary Studies; Behavior; Biomarker Development; Comparative Effectiveness Research; Epidemiology; Health Disparities; Interventional Trial; Pediatrics; Racial Disparities; Translation; Transplantation; Women's Health; Genetics and Genomics; Imaging and Biotechnology; Immunology and Inflammation; Systems Biology; Bioinformatics; Integrative biology; Omics; Pharmacogenomicshttp://www.dknet.org/Margolis, Ronald (NIH/NIDDK) [E]NoNoNo4/16/2014 3:43 PM

The NIDDK Information Network (dkNET), serves the needs of basic and clinical investigators by providing seamless access to large pools of data relevant to the mission of NIDDK. The goal of dkNET is to develop a community-based network for integration across disciplines to include the larger DK universe of diseases, investigators, and potential users. dkNET seeks to interconnect basic science consortia as a first step in moving toward development of a more comprehensive and broadly applicable DK-specific biomedical informatics resource.

Research Materials268
  
Mutant Mouse: Smad4Animal ModelsDevelopmental Biologyhttp://www.ncbi.nlm.nih.gov/pubmed/16330325
Deng, Chuxia (NIH/NIDDK) [E]
YesYesYes4/4/2014 9:56 AM

Smad4 conditional KO.  Inactivation of LoxP-flanked Smad 4 makes it possible to explore the role of Smad 4 in embryonic development of different tissues and in tumorigenesis.

 

Members of the TGF-b superfamily (which includes Bone Morphogenic Protein and Activin as well as TGF-b ) bind to and activate specific receptors, which activate receptor Smads (Smad 2/3 or Smad 1/5/8), which activate the common SMAD, SMAD 4.  Smad4 -/- mice die early in embryogenesis.  Floxed Smad4 exon 8 mutants were prepared so that Smad 4 could be conditionally disrupted when the floxed mice were mated with mice expressing a Cre recombinase that is expressed in particular tissues, at a particular time, or both.  The conditional knockout strategy makes it possible to explore the role of Smad 4 in embryonic development of different tissues (e.g., neural crest, retina, heart) and in tumorigenesis (pancreatic and head and neck cancers, interactions with oncogenes and tumor suppressors).

Research Materials271
  
Mutant Mouse: Smad4Animal ModelsDevelopmental Biologyhttp://www.ncbi.nlm.nih.gov/pubmed/9520423
Deng, Chuxia (NIH/NIDDK) [E]
YesYesYes4/4/2014 9:56 AM

Smad4 knockout: Smad 4 is essential for epiblast proliferation and mesoderm induction in early embryogenesis.

 

The TGF-β-related superfamily plays an important role in multiple biological systems including embryogenesis.  TGF-β ligands activate specific receptors, which interact with specific Smad proteins, which in turn form a complex with a common partner, Smad4, that conveys the signal to downstream targets.  Exon 8 of the Smad4 gene was disrupted using homologous recombination in embryonic stem cells.  Exon 8 encodes the C-terminal domain of Smad4 that is essential for the formation of heteromeric complexes with the other Smads.  Mice heterozygous for the Smad4 mutation are phenotypically normal.  Homozygotes, however, die early in embryonic development (day E6.5-8.5). Smad4 is required for three essential functions in early embryogenesis: epiblast proliferation, egg cylinder formation, and mesoderm induction.

Research Materials274
  
Mutant Mouse:  Smad3 (MAD homolog 3 (Drosophila))Animal ModelsImmunology and Inflammationhttp://www.ncbi.nlm.nih.gov/pubmed/10064594
Deng, Chuxia (NIH/NIDDK) [E]
YesYesYes4/4/2014 9:55 AM

Smad 3 knockout: Increased susceptibility to opportunistic infections and massive abscesses result from impaired TGF-β-mediated regulation of T cell activation and mucosal immunity.

 

Smad3 is one of the intracellular mediators that transduce signals from transforming growth factor beta (TGF-β) and activin receptors to the common Smad, Smad4.  Targeted disruption of exon 8 in the Smad3 gene deletes a C-terminal region of the protein that is essential for interacting with the TGF-β receptor.  The Smad3 null mice are viable at birth, but at weaning develop a progressive and ultimately lethal illness characterized by massive abscesses caused by bacteria that only are infectious in the context of immune deficiency.  The immune defect is attributed to abnormalities in mutant T cells and neutrophils.  Mutant T cells exhibited an activated phenotype in vivo, and were resistant to inhibition by TGF-β.  Mutant neutrophils were impaired in their chemotactic response to TGF-β.  Smad-3 plays an important role in TGF-β-mediated regulation of T cell activation and mucosal immunity that can increase susceptibility to opportunistic infection.

Research Materials273
  
Mutant Mouse:  Sirt6Hematologic DiseaseAnimal Modelshttp://www.ncbi.nlm.nih.gov/pubmed/20816089
Deng, Chuxia (NIH/NIDDK) [E]
YesYesYes4/4/2014 9:55 AM

Generation of floxed Sirtuin 6 for the construction of conditional knockout mice

 

The Sirtuins (Sirt1-7), a family of seven proteins related to yeast Sir2, are histone deacetylases that regulate many critical biological processes including genomic stability, adaptation to calorie restriction and aging.  Mice with a targeted disruption of Sirt6 had very low levels of blood glucose (and paradoxically, low insulin levels) and died shortly after weaning.  Hypoglycemia, attributed to increased sensitivity to insulin, was the major cause for lethality.

 

Because of the post-weaning mortality of Sirt6 null mice, liver-specific Sirt6 conditional knockout mice were constructed using Cre-Lox technology to study the effects on glucose and lipid metabolism.  Hepatic-specific Sirt6 deficient mice exhibited increased glycolysis and triglyceride synthesis, resulting in the development of fatty liver.  Sirt6 is a potential therapeutic target for treating fatty liver disease, the most common cause of liver dysfunction.

Research Materials278
  
Mutant Mouse:  Sirt3Endocrine Disease and Metabolic DiseaseAnimal Modelshttp://www.ncbi.nlm.nih.gov/pubmed/20129246
Deng, Chuxia (NIH/NIDDK) [E]
YesYesYes4/4/2014 9:55 AM

Sirt3 KO: Sirt3 is a mitochondrial-localized tumor suppressor that maintains mitochondrial integrity and metabolism during stress.

 

SirT3 is a mitochondrial protein that is a member of the Sirtuin family of NAD-dependent protein deacetylases.  Sirt3(-/-) mice are phenotypically normal, but exhibit many proteins whose acetylation is increased.  They generate more reactive oxygen species and are more susceptible to mammary tumors than normal mice.   Sirt3 is inactivated in a large percentage of human breast and ovarian cancers, suggesting that Sirt3 may be a mitochondria-localized tumor suppressor by maintaining mitochondrial integrity and efficient oxidative metabolism.

Research Materials272
  
Mutant Mouse:  Sirt1Hematologic DiseaseAnimal Modelshttp://www.ncbi.nlm.nih.gov/pubmed/21103071http://www.jci.org/articles/view/46243
Deng, Chuxia (NIH/NIDDK) [E]
YesYesYes4/4/2014 9:55 AM

Generation of floxed Sirtuin 1 Exon5-Exon6 for the construction of conditional knockout mice

 

Sirtuin 1 (Sirt1), a homolog of yeast Sir 2, is an NAD-dependent histone and protein deacetylase.  It has a wide range of biological functions, ranging from DNA damage repair to effects on glucose metabolism.  Sirt1 null mice die before birth due to chromosomal aberrations and impaired DNA damage repair.  Sirt1 is thought to affect energy metabolism, but the mechanism remains poorly understood.  In order to study tissue-specific metabolic effects of Sirt1, floxed Sirt1 was constructed so that exons 5 and 6 would be deleted using the Cre-Lox strategy.  In contrast to a previously reported deletion of Sirt1 exon4, no truncated (and potentially active) Sirt1 forms were detected when exons 5 and 6 were deleted.

 

Hepatic exon 5-6 null Sirt1 mice were generated when Floxed Sirt1 exon 5 and 6 mice were mated with mice that expressed the Cre-recombinase in liver.  The hepatic exon 5-6 null Sirt1 mice developed fatty liver under normal feeding conditions.  This was accompanied by increased expression of the carbohydrate responsive element binding protein, which is a major regulator of lipid synthesis1.  Sirt1-deficient liver also has an impaired insulin response, primarily due to reduced phosphorylation of the serine-threonine kinase Akt in the presence of insulin.2

Research Materials277
  
Mutant Mouse:  Sirt1 (sirtuin 1 (silent mating type information regulation 2, homolog) 1 (S. cerevisiae)Endocrine Disease and Metabolic DiseaseAnimal Modelshttp://www.ncbi.nlm.nih.gov/pubmed/18835033
Deng, Chuxia (NIH/NIDDK) [E]
YesYesYes4/4/2014 9:55 AM

Sirt1 knockout: Sirt1, a protein deacetylase, is a tumor suppressor that promotes genome stability and regulates proteins involved in energy metabolism.

 

Yeast Sir2, a nicotinamide adenine dinucleotide (NAD)-dependent protein deacetylase, has been implicated in chromatin silencing, longevity and genome stability.  Mammals contain a family of related deacetylases, the sirtuins, of which 7 have been identified.  Sirt1 is the closest mammalian orthologue of yeast Sir 2.  The Sirt1 gene in mice was disrupted by homologous recombination in embryonic stem cells.  The majority of Sirt1 (-/-) embryos die between E9.5 and E14.5, displaying altered histone modification, increased chromosomal aberrations, and impaired DNA damage repair. Tumor formation was increased in mutant tissues in Sirt1(+/-): p53(+/-) double heterozygotes, indicating that full levels of Sirt1 are necessary for tumor suppression.  Tumorigenesis is reduced by treatment with the polyphenol, resveratrol, which activates Sirt1.  Sirt1 may act as a tumor suppressor by promoting DNA damage repair and maintaining genome integrity.  Sirt1also is involved in the regulation of proteins involved in energy metabolism, and components of the circadian clock.

Research Materials301
  
Mutant Mouse:   s1pr3Animal ModelsDevelopmental Biologyhttp://www.ncbi.nlm.nih.gov/pubmed/15138255
Proia, Richard (NIH/NIDDK) [E]
YesYesYes4/4/2014 9:54 AM

A Spingosine-1-phosphate Receptor-3 (S1pr3) knockout mouse

Sphingosine-1-phosphate (S1P), a sphingolipid metabolite, activates cell signaling by interacting with a family of G-protein-coupled cell-surface S1P receptors that activate different and overlapping signaling pathways.  Three S1P receptors (S1P1, S1P2 and S1P3) are abundant in embryonic endothelial cells.  SIP1 knockouts are embryonic lethals because of hemorrhage, but neither S1P2 null mice nor S1P3 null mice were embryonic lethals.  Double null embryos (S1P2 S1P3) and triple null embryos (S1P1 S1P2 S1P3), however, displayed a more severe vascular phenotype than did S1P1 null embryos, suggesting that S1P2 and S1P3 receptors act cooperatively.

Research Materials300
  
Mutant Mouse:  S1pr2Animal ModelsDevelopmental Biologyhttp://www.ncbi.nlm.nih.gov/pubmed/15138255
Proia, Richard (NIH/NIDDK) [E]
YesYesYes4/4/2014 9:54 AM

A Spingosine-1-phosphate Receptor-2 (S1pr2) knockout mouse



Sphingosine-1-phosphate (S1P), a sphingolipid metabolite, activates cell signaling by interacting with a family of G-protein-coupled cell-surface S1P receptors that activate different and overlapping signaling pathways.  Three S1P receptors (S1P1, S1P2 and S1P3) are abundant in embryonic endothelial cells.  S1P1 knockouts are embryonic lethals because of hemorrhage.  S1P2 null mice did not exhibit embryonic lethality or phenotypic abnormalities.  However, double null embryos (S1P1 S1P2 and S1P2 S1P3), and triple null embryos (S1P1 S1P2 S1P3) displayed a more severe vascular phenotype than did S1P1 null embryos, suggesting cooperative functions of the three S1P receptors.

Research Materials303
  
Mutant Mouse:  S1pr1Animal ModelsDevelopmental Biologyhttp://www.ncbi.nlm.nih.gov/pubmed/12869509
Proia, Richard (NIH/NIDDK) [E]
YesYesYes4/4/2014 9:54 AM

A conditional knockout mouse for S1pr1

 

Sphingosine-1-phosphate (S1P) is a potent bioactive lipid that activates a family of G-protein coupled receptors, S1P1, S1P2, S1P3, S1P4 and S1P5. The S1P1 receptor is widely expressed and has critical functions in the immune, cardiovascular and nervous systems.  It is a target for Fingolimod (brand name: Gilenya™), an immunomodulating drug, FDA approved for treating multiple sclerosis. The S1pr1 knockout mouse and the S1pr1 floxed mouse are useful for studying the function of the S1P1 receptor.

 

Mice with a floxed S1P1 receptor gene were mated with mice expressing Cre-recombinase only in endothelial cells to disrupt the S1P1 gene exclusively in endothelial cells.  The phenotype of the conditional mutant embryos was indistinguishable from the phenotype of S1P1 null embryos in which the S1P1 receptor was disrupted in all cells.  These results indicate that S1P1 receptors in endothelial cells direct the coverage of embryonic blood vessels by vascular smooth muscle cells.

Research Materials299
  
Mutant Mouse:  S1pr1 (spingosine-1-phosphate receptor 1)Animal ModelsImmunology and Inflammationhttp://www.ncbi.nlm.nih.gov/pubmed/11032855
Proia, Richard (NIH/NIDDK) [E]
YesYesYes4/4/2014 9:54 AM

A Sphingosine-1-phosphate Receptor-1 (S1pr1) knockout mouse

 

Sphingosine-1-phosphate (S1P) is a potent bioactive lipid that activates a family of G-protein coupled receptors, S1P1, S1P2, S1P3, S1P4 and S1P5. The S1P1 receptor is widely expressed and has critical functions in the immune, cardiovascular and nervous systems.  It is a target for Fingolimod (brand name: Gilenya™), an immunomodulating drug, FDA approved for treating multiple sclerosis. The S1pr1 knockout mouse and the S1pr1 floxed mouse are useful for studying the function of the S1P1 receptor.

Research Materials294
  
Mutant Mouse: Bcl2l1(Bcl2-like 1)Animal ModelsDevelopmental Biologyhttp://www.ncbi.nlm.nih.gov/pubmed/10894153
Hennighausen, Lothar Dr. (NIH/NIDDK) [E]
YesYesYes4/4/2014 9:53 AM

Floxed Bcl-x: Conditional knockout of pro-survival Bcl-x in primordial germ cells was used to study the balance between pro-aptoptotic Bax during embryogenesis.


Bcl-x is a pro-survival protein that opposes the pro-apoptotic action of Bax which interacts with mitochondria to activate the caspase 9 pathway.  Mice in which the Bcl-x gene is inactivated die at E12.5.  To be able to study lineage-specific activites of Bcl-x at different stages of development, the Cre-LoxP recombination system was used.  Homologous recombination was used to flank the promoter, exon1, and major coding exon2 of the Bcl-x gene with loxP sites.  The targeted allele contained a loxP flanked (or floxed) neomycin cassette in the Bcl-x promoter, and an additional loxP site in intron 2.  Floxed Bcl-x has been used to study the balance between Bcl-x and Bax in primordial germ cells that undergo controlled levels of cell reduction due to apoptosis, the induction of hemolytic anemia and splenomegaly following conditional deletion of the Bcl-x gene from erythroid cells, the protection of hepatocytes from apoptosis and ensuing fibrotic response by Bcl-x, and the demonstration that Bcl-x is critical for the survival of dendritic cells, important regulators of immune function.

Research Materials276
  
Mutant Mouse:  Brca1 (Breast cancer1)Animal ModelsDevelopmental Biologyhttp://www.ncbi.nlm.nih.gov/pubmed/10319859http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3247816/
Deng, Chuxia (NIH/NIDDK) [E]
YesYesYes4/4/2014 9:53 AM

BRCA1 conditional knockouts.  BRCA1 LoxP mutations allow selective inactivation of the gene in mammary epithelial cells (accelerating breast tumor formation) and in cardiomyocytes (impairing cardiac remodeling that may increase the risk of heart failure following myocardial infarction).

 

Although germ-line mutations of BRCA1 increase susceptibility to familial breast and ovarian cancer, embryonic lethality of BRCA1 null mutations in mice precluded study of the role of BRCA1 in mammary gland development and neoplasia.  To make it possible to study BRCA1 function in different tissues at different stages of development, conditional mutants in exon11 of the BRCA1 gene were constructed using the Cre-Lox approach.  Cre-mediated excision of exon 11 of Brca1 in mouse mammary epithelial cells caused increased apoptosis, abnormal ductal development, and mammary tumor formation after a long latency.1  The formation of mammary tumors was accelerated in female mice in which Brca1 had been selectively inactivated in mammary epithelial cells when an inactive p53 gene also was introduced.  Cre-mediated excision of floxed BRCA1 in mouse cardiomyocytes impairs cardiac remodeling, leading to poor ventricular function and higher mortality in response to ischaemic or genotoxic stress, suggesting that BRCA1 mutations in humans may increase the risk of cardiac failure2.

Research Materials275
  
Mutant Mouse:  Brca1 (Breast cancer1)Animal ModelsDevelopmental Biologyhttp://www.ncbi.nlm.nih.gov/pubmed/9872327
Deng, Chuxia (NIH/NIDDK) [E]
YesYesYes4/4/2014 9:53 AM

Knockout of the BRCA1 (Breast Cancer 1) gene impairs DNA damage repair resulting in embryonic death.

 

Germ-line mutations of the nuclear protein BRCA1 are responsible for increased susceptibility to familial breast and ovarian cancers.  Targeted mutation of exon 11 of mouse BRCA1 results in embryonic lethality early in embryogenesis.  Embryos containing a Brca1 null mutation are hypersensitive to gamma irradiation and exhibit structural DNA damage, supporting a role for BRCA1 in DNA damage repair.  The chromosomal abnormalities were more massive in a p53 null background, suggesting that the loss of p53 acting at cell cycle checkpoints allows cells with damaged DNA to accumulate.  The additional mutations may account for the tumorigenesis associated with Brca1 mutations in humans.

Research Materials279
  
Mutant Mouse: Fgfr1 (Fibroblast Growth Factor Receptor 1)Animal ModelsDevelopmental Biologyhttp://www.ncbi.nlm.nih.gov/pubmed/16207751
Deng, Chuxia (NIH/NIDDK) [E]
YesYesYes4/4/2014 9:53 AM

FGFR1 conditional knockouts.  Inactivation of FGFR1 LoxP in limb mesenchyme early in embryogenesis shows that FGFR1 is indispensable for normal limb development

 

Fibroblast Growth Factor Receptor 1 (FGFR1) is primarily expressed in the mesenchyme of developing limb buds, and mutant FGFR1 genes in human patients are associated with abnormalities in distal limb structures.  Since traditional knockout of FGFR1 is lethal soon after implantation, conditional knockout of the FGFR1 gene in limb mesenchyme at early stages of embryonic development using the Cre-LoxP approach was used to study the role of FGFR1 in limb development.  FGFR1 is dispensable for limb initiation, but plays an indispensable role in the very early stages of proximal-distal development of the limb. Expression of several signaling candidate genes that may be involved in digit patterning is altered.

Research Materials269
  
Mutant Mouse: Fgfr2 KO (Fgfr2 tm1Cxd)  MouseAnimal ModelsDevelopmental Biologyhttp://www.ncbi.nlm.nih.gov/pubmed/9435295
Deng, Chuxia (NIH/NIDDK) [E]
YesYesYes4/4/2014 9:52 AM

FGFR2 knockout is an embryonic lethal mutation and blocks limb bud initiation.

 

Fibroblast Growth Factor Receptor 2 (FGFR2) is a high affinity receptor for several members of the FGF family.  The FGFR2 gene was inactivated by deleting the entire immunoglobulin-like domain of the receptor which is critical for FGF binding and FGFR2 activity.  Embryos that lack this domain die at E10-11.5 owing to a failure in chorioallantoic fusion or placental formation. The deletion also blocks limb bud initiation, establishing FGFR2 as the major receptor that mediates FGF signals during limb induction.

Research Materials10
  
Mutant Mouse:  Fgfr3Animal ModelsDevelopmental Biologyhttp://www.ncbi.nlm.nih.gov/pubmed/8601314
Deng, Chuxia (NIH/NIDDK) [E]
YesYesYes4/4/2014 9:52 AM

FGFR3 knockout. Complete knockout of the FGFR3 gene, the gene in which missense mutants cause short statue achrondorplasia, fails to restrain cartilage growth at the bone growth plate, allowing bones to elongate excessively but fail to ossify.

 

Endochondral ossification is a major mode of bone formation. Cartilage proliferates, undergoes hypertrophy, begins to calcify, undergoes a program of cell death, and is replaced by osteoblasts. Fibroblast Growth Factor Receptor 3 (FGFR3) is expressed in cartilage rudiments of a wide variety of bones, and dominant missense mutations in the human FGFR3 gene cause achondroplasia, a common form of human dwarfism characterized by minimal proliferation of the growth plate cartilage in long bones. To determine the effect of complete absence of FGFR3 on bone development in mice, targeted disruption of the FGFR3 gene was accomplished by homologous recombination in embryonic stem cells. Remarkably, the vertebral column and long bones of FGFR3 null mice were extremely long, suggesting that in normal development, FGFR3 restrains cartilage promotion and limits bone elongation so that the endochondral ossification program can proceed. Restraint of cartilage growth by FGFR3 provides a plausible explanation for the role of FGFR3 missense mutations in human achondroplastic dwarfs.

Research Materials280
  
Mutant Mouse:  Fgfr4Animal ModelsDevelopmental Biologyhttp://www.ncbi.nlm.nih.gov/pubmed/9716527
Deng, Chuxia (NIH/NIDDK) [E]
YesYesYes4/4/2014 9:52 AM

FGFR4 knockout: Lung alveoli fail to develop normally in double mutant with FGFR4 and FGFR3 knockouts

 

The Fibroblast Growth Factor Receptor (FGFR) 4 gene was inactivated by targeted disruption and homozygous recombination to study its possible role in lung development. FGFR-4 is expressed in postnatal lung, and FGFR-4 null mice have no obvious abnormalities.  However, mice that are doubly homozygous for targeted disruptions of FGFR3 and FGFR4 display novel phenotypes, including pronounced dwarfism and lung abnormalities.  The lungs of the double knockout mice are normal at birth, but they fail to develop secondary septae that delimit alveoli and increase the surface area of the lung.  Although lung function is impaired, the double homozygous knockout mice are viable but sickly.

Research Materials304
  
Mutant Mouse:  Gba (glucosidase, beta, acid).Knock-in P444L ±A456P mimic Gaucher disease.Animal ModelsDevelopmental Biologyhttp://www.ncbi.nlm.nih.gov/pubmed/9482915
Proia, Richard (NIH/NIDDK) [E]
YesYesYes4/4/2014 9:52 AM

Gba-444 knock-in mice carrying the milder L444P Gaucher disease mutation (Gba-L444P mice) and the severe Gaucher disease mutation (Gba-L444P A456P mice)

 

Gba-L444P and Gba-L444P A456P mice, respectively, carry common gene mutations for milder or severe Gaucher disease, a lysosomal storage disease.  Gaucher Disease is caused by mutations in the lysosomal enzyme, glucocerebrosidase.  Deficiency of enzyme activity leads to the accumulation of glucosylceramide in liver, spleen, bone, and in the most severe cases, the central nervous system.  A single insertion mutagenesis procedure was used to introduce mutations found in human Gaucher Disease into the mouse glucocerebrosidase gene.  Mice homozygous for the double mutation L444P A456P had little enzyme activity and accumulated glucosylceramide in brain and liver.  Mice homozygous only for the L444P mutation seen in a milder chronic form of Gaucher disease had higher levels of enzyme activity and did not accumulate glucosylceramide in brain and liver.  Mice with either point mutation died within 48 h of birth.

 

The mice can be useful for the study of disease pathogenesis and for devising new therapies.  These include but are not restricted to gene transfer therapy, enzyme replacement therapy, cell replacement therapy and small molecule therapy (synthesis inhibitors, enzyme activators).

Research Materials286
  
Mutant Mouse:  Chrm1 (Cholinergic Receptor, muscarinic 1)Animal ModelsDevelopmental Biologyhttp://www.ncbi.nlm.nih.gov/pubmed/11856534
Wess, Hans-Jurgen (NIH/NIDDK) [E]
YesYesYes4/4/2014 9:51 AM

M1 Muscarinic Receptor Knockout: support involvement in cognitive processes

 

The five Muscarinic Acetylcholine (ACh) receptors are G-protein coupled receptors (M1R-M5R). M1R, M3R and M5R selectively couple to Gq/G11; M2R and M4R selectively couple to Gi/Go.  M1R knockout mice are viable and fertile, and have no major morphological abnormalities.

 

M1 muscarinic receptors are located in higher brain regions of the central nervous system that are involved in cognitive processes.  Studies in M1R knockout mice show that M1 receptors may be involved in cortical memory functions that require interactions between the cerebral cortex and hippocampus. Supporting a role for M1 receptor activation in cognition, muscarinic agonist-induced activation of the MAPK pathway, which plays an important role in synaptic plasticity and many cognitive functions, is virtually abolished in primary cortical cultures or CA1 hippocampal pyramidal neurons in M1R knockout mice.

Research Materials287
  
Mutant Mouse:  Chrm2Animal ModelsDevelopmental Biologyhttp://www.ncbi.nlm.nih.gov/pubmed/11392613
Wess, Hans-Jurgen (NIH/NIDDK) [E]
YesYesYes4/4/2014 9:51 AM

M2 Muscarinic Receptor Knockout: role in learning and memory, and mediating analgesic effectsof muscarinic agonists

 

The five Muscarinic Acetylcholine (ACh) receptors are G-protein coupled receptors (M1R-M5R). M1R, M3R and M5R selectively couple to Gq/G11; M2R and M4R selectively couple to Gi/Go.  M2R knockout mice are viable and fertile, and have no major morphological abnormalities.

 

M2 muscarinic receptors are located in the central nervous system and the periphery.  Studies with M2R knockout mice strongly suggest that the M2 receptor is the key presynaptic muscarinic receptor mediating the inhibition of hippocampal and cortical ACh release.  Studies with M2R knockout mice suggest that central M2Rs play important roles in learning and memory.  The M2R mediates ACh-mediated reductions in heart rate.  Analysis of M2R knockout mice also has shown that the analgesic effects observed after administration of muscarinic agonists are mediated primarily by M2Rs.

Research Materials285
  
Mutant Mouse: M3 Muscarinic receptor KO (Chrm3 tm1Jwe)  MouseEndocrine Disease and Metabolic DiseaseAnimal Modelshttp://www.ncbi.nlm.nih.gov/pubmed/11242080
Wess, Hans-Jurgen (NIH/NIDDK) [E]
YesYesYes4/4/2014 9:51 AM

M3 Muscarinic Receptor Knockout mice are hypophagic, lean, and have improved glucose tolerance and insulin sensitivity.

 

The five Muscarinic Acetylcholine (ACh) receptors are G-protein coupled receptors (M1R-M5R). M1R, M3R and M5R selectively couple to Gq/G11; M2R and M4R selectively couple to Gi/Go.  M3 muscarinic ACh receptors are present in the central nervous system and the periphery.

 

M3R knockout mice are viable and fertile, and have no major morphological abnormalities.  They have a lean phenotype.  This results from a combination of reduced caloric intake and increased energy expenditure.  They eat less food than wild-type mice, possibly because a central cholinergic pathway that stimulates food intake is disrupted. They also expend more energy. Because of their lean phenotype, M3R knockout mice have improved glucose tolerance and increased insulin sensitivity.  Pharmacological blockade of central M3Rs may be a novel strategy for the treatment of obesity and associated metabolic disorders.

 

In the airway, vagally-mediated bronchoconstriction responses were abolished in M3R knockout mice in vivo, suggesting that M3R antagonists may be useful in the treatment of chronic obstructive pulmonary disease (COPD) and asthma.  Studies with M3R knockout mice also have shown that the M3R is the major muscarinic receptor mediating ACh-induced glandular secretion from exocrine and endocrine glands, including the secretion of insulin from pancreatic beta cells.

Research Materials288
  
Mutant Mouse:  Chrm4Animal ModelsBehaviorhttp://www.ncbi.nlm.nih.gov/pubmed/10468635
Wess, Hans-Jurgen (NIH/NIDDK) [E]
YesYesYes4/4/2014 9:51 AM

M4 Muscarinic Receptor Knockout: Activation of M4R may reduce the reinforcing effect of drugs of abuse, and contribute to the analgesic effects observed after administration of muscarinic agonists.

 

The five Muscarinic Acetylcholine (ACh) receptors are G-protein coupled receptors (M1R-M5R). M1R, M3R and M5R selectively couple to Gq/G11; M2R and M4R selectively couple to Gi/Go.  M4R knockout mice are viable and fertile, and have no major morphological abnormalities.

 

Dopamine hyperactivity in subcortical areas such as the nucleus accumbens is a key feature associated with schizophrenia.  M4 muscarinic receptors in the central nervous system are decreased in the basal ganglia and prefrontal cortex of patients with schizophrenia, and basal dopamine levels are increased in the nucleus accumbens of M4R knockout mice.  These results suggest that M4R agonists may be clinically useful in the treatment of schizophrenia and other CNS disorders associated with hyperdopaminergia.

 

Most drugs of abuse trigger an increase in dopamine release in the nucleus accumbens.  Stimulation of midbrain M4 autoreceptors are thought to decrease the activity of dopaminergic neurons in ventral tegmental area neurons, leading to reduced dopamine release in the nucleus accumbens.  Activation of central M4R may reduce the reinforcing effects of drugs of abuse.  Analysis of M4R knockout mice also has shown that M4Rs contribute to the analgesic effects observed after administration of muscarinic agonists.

Research Materials289
  
Mutant Mouse:  Chrm5Animal ModelsBehaviorhttp://www.ncbi.nlm.nih.gov/pubmed/12675128
Wess, Hans-Jurgen (NIH/NIDDK) [E]
YesYesYes4/4/2014 9:50 AM

M5 Muscarinic Receptor Knockout: Deficiency of M5Rs reduces drug-seeking behavior

 

The five Muscarinic Acetylcholine (ACh) receptors are G-protein coupled receptors (M1R-M5R). M1R, M3R and M5R selectively couple to Gq/G11; M2R and M4R selectively couple to Gi/Go.  M5R knockout mice are viable and fertile, and have no major morphological abnormalities.

 

M5 muscarinic ACh receptors are located in the central nervous system and may contribute to the cognitive-enhancing effects of ACh.  M5R knockout mice show deficits in two hippocampus-dependent cognitive tasks, and exhibit reduced cerebral blood flow in the cerebral cortex and hippocampus, consistent with the observation that M5Rs mediate ACh-mediated dilation of cerebral blood vessels.  M5R agonists or agonists for mixed M1/M5 receptors may be effective in the treatment of Alzheimer’s disease and related memory disorders.  The M5R knockout mutation also appears to exert a stabilizing effect on sensorimotor gating in intact mice, which is decreased in schizophrenia.  Analysis of M5R knockout mice also has shown that the lack of M5Rs reduces drug-seeking behavior.

Research Materials281
  
Mutant Mouse:  human erythropoietin receptor transgene bred onto a mouse erythropoietin receptor null backgroundAnimal ModelsRacial Disparitieshttp://www.ncbi.nlm.nih.gov/m/pubmed/11435319/
Noguchi, Connie (NIH/NIDDK) [E]
YesYesYes4/4/2014 9:50 AM

mEpoR-/- hEpoR+: The mouse Erythropoietin Receptor knockout that contains a human Erythropoietin Receptor transgene can be used to define the potency of recombinant erythropoietin preparations used to treat anemia associated with chronic kidney disease an

 

Erythropoietin, acting by binding to Erythropoietin receptors (EpoR) on erythroid progenitor cells, is required for erythropoiesis.  Absence of erythropoietin or the EpoR in mice interrupts erythropoiesis in the fetal liver and result in death at embryonic day 13.5.  An 80-kb human EpoR transgene bred onto a mouse EpoR null background (provided by F. Constantini of Columbia University) restored effective erythropoiesis in the EpoR null mouse.  Erythropoietin preparations made utilizing recombinant DNA technology are used in the treatment of anemia in chronic kidney disease and other critical illnesses.  The mouse EpoR null mouse containing the human EpoR transgene can be used to define the potency of erythropoietin preparation in humans.

Research Materials283
  
Mutant Mouse:  The tet transactivator (rtTA) gene placed under the control of the human NPHS2 gene).Animal ModelsRacial Disparitieshttp://www.ncbi.nlm.nih.gov/pubmed/12874453
Kopp, Jeffrey, Dr. (NIH/NIDDK) [E]
YesYesYes4/4/2014 9:50 AM

Reverse tetracycline-controlled transgenic mouse model (Tet-On) under the control of the specific promoter for the glomerular podocyte protein (Podocin, NPHS2)

 

Podocytes are post-mitotic epithelial cells that are positioned on the exterior aspect of the glomerular capillary wall and contribute to the selective molecular permeability of glomeruli.  Podocyte damage or dysfunction results in loss of the characteristic foot processes that normally interdigitate and form the selective permeability barriers composed of filtration slits bridged by slit diaphragms.  Minimal damage causes proteinuria that, in the case of minimal change disease (MCD), can be reversed by steroid treatment.  In focal segmental glomerulosclerosis, more severe loss of podocytes ultimately results in glomerulosclerosis.

 

The transgenic mouse model described uses a tetracycline controlled reporter-operator system from E. coli to induce the transcription of a target gene in podocytes.  Transcription is induced only in podocytes and only when tetracycline is administered.  The response is dependent on the tetracycline dose.  The podocyte-specific inducible transgene system can be used to identify factors that exacerbate or ameliorate podocyte injury, and can be used to express Cre-recombinase.

 

In the reverse tetracycline-controlled transcriptional activator system (rtTA), transcription in podocytes is activated by a transgene expressing a chimeric protein containing: (i) the promoter-enhancer region of Nphs2 (podocin, a protein specifically expressed in the podocyte), (ii) a Tet repressor domain that only binds to and activates the tetracycline operator sequence (TetO) when it binds tetracycline, and (iii) a VP16 activation domain. The target gene to be induced is linked to the tetracycline operator (TetO).

Research Materials305
  
Mutant Mouse:  Sphk2 (Sphingosine Kinase 2)Animal ModelsImmunology and Inflammationhttp://www.ncbi.nlm.nih.gov/pubmed/16314531
Proia, Richard (NIH/NIDDK) [E]
YesYesYes4/4/2014 9:50 AM

A knockout mouse for Sphingosine kinase 2 (Sphk2)

Sphingosine kinase 1 and 2 are enzymes that produce sphingosine-1-phosphate (S1P), a potent bioactive compound that activates a family of G-protein coupled receptors known as S1P receptors.  Triggering these receptors on cells has important effects related to inflammation, immunity, cancer, angiogenesis, cell proliferation, adhesion, cardiovascular function, nervous system function and injury responses.  Sphingosine kinase 1 is the predominant isozyme for extracellular S1P production.  Sphingosine kinase 2 is the predominant isozyme that activates fingolimod (brand name: Gilenya™), an immunomodulating drug that has been approved by the FDA for treating multiple sclerosis. The sphingosine kinase 1 knockout mouse and the sphingosine kinase 2 knockout mouse will be valuable for determining the functions of sphingosine-1- phosphate and S1P receptors.  These mice will also be useful for the study of fingolimod and related compounds.  SPHK2 is a more potent activator of fingolimod than SPHK1.

Research Materials9
  
http://www.ott.nih.gov/technology/e-063-20120
Hall, Kevin (NIH/NIDDK) [E]
YesYesYes4/4/2014 9:49 AM

Attempts to manage body weight are often unsuccessful or only temporary. This is, in part, due to antiquated dieting methods that attempt to address calorie consumption while ignoring metabolic and physical changes. It is becoming clear that personalized methods to manage body weight must be developed.

 

Scientists at the NIH have developed new methods for prescribing and monitoring personalized weight management interventions. The system uses validated mathematical models of human metabolism to set weight management goals and predict individual body weight outcomes in the context of changing metabolic needs and calorie consumption. The system uses repeated monitoring of a patient's body weight to assess progress and provide specific feedback to the patient and health care professional. Projected outcomes and body weight goals can be revised over time along with required prescription modifications to meet the body weight goals. The system is integrated into a network of one or more devices that may additionally monitor various physiological parameters, physical activities, food intake, or other behaviors. Such an enhanced personalized weight management program has great promise in the management of obesity.

Research Materials266
  
http://bwsimulator.niddk.nih.gov/http://www.ott.nih.gov/technology/e-160-20120http://www.ncbi.nlm.nih.gov/pubmed?term=21872751Kevin Hallkevinh@niddk.nih.gov
Hall, Kevin (NIH/NIDDK) [E]
YesYesYes4/4/2014 9:49 AM

Known methods for predicting weight loss fail to account for slowing of metabolism as weight is lost and therefore overestimate the degree of weight loss. While this limitation of the 3500 Calorie per pound rule has been known for some time, it was not clear how to dynamically account for the metabolic slowing. The invention provides a Java applet for modeling of human metabolism to improve the weight change predictions. The model has been validated using previously published human data and the model equations have been published. A web-based implementation of the published dynamic model has been created to allow users to perform simulations for planning weight loss interventions in adults and accounts for individual differences in metabolism and body composition. Values to the user include being able to see whether the target weight loss is realistic when the necessary caloric restriction, exercise and timeframe components are highlighted. Unrealistic goals become apparent. More moderate goals may result in greater long term success. The model also defines the caloric intake to be followed once the new weight target has been met to prevent weight being regained.

Research Materials347
  
www.google.com/patents/US20090054476
Gao, Zhanguo (NIH/NIDDK) [E]
YesYesNo4/4/2014 9:48 AM
The present invention relates to allosteric modulation of A3 adenosine receptor (A3AR) and provides for the use of an A3 adenosine receptor modulator (A3RM), for the preparation of pharmaceutical compositions for modulating the A3AR in a subject, as well as pharmaceutical compositions comprising the same and therapeutic methods comprising administering to a subject an amount of an A3RM, the amount being effective to modulate A3AR activity. The A3RM according to the invention are 1H-Imidazo-[4,5-c]quinolin-4-amine derivatives. The invention also provides some of such novel 1H-Imidazo-[4,5-c]quinolin-4-amine derivatives.
Research Materials350
  
https://www.google.com/patents/US20120252823
Jacobson, Kenneth (NIH/NIDDK) [E]
YesYesYes4/4/2014 9:48 AM
NIDDK announces the availability of  a highly selective A1 adenosine receptor (AR) agonist.  This receptor is neuroprotective in ischemic and epileptic models.  The A1AR-selective full agonist MRS5474  displayed anticonvulsant activity in vivo in a model of minimal clonic seizures, without toxicity characteristic of other A1AR agonists. Nucleoside docking to a homology model based on recently reported agonist-bound AR structures characterized the interaction of cycloalkylrelated constituents with a small hydrophobic subpocket in the A1AR.  Recent advances in specificity to the A1AR encourage development of these agonists for CNS disorders. Work on the structure activity relationship of candidate molecules and the human A1AR revealed that  substituents larger than cyclobutyl greatly reduced the AR affinity, and groups that were much larger or smaller than cyclopropyl abolished A1AR selectivity. The group of truncated derivatives that were developed have more drug-like physical properties than other A1AR agonists; this approach is appealing for preclinical development. 
Research Materials331
  
Adenovirus gene expression system
Gershengorn, Marvin (NIH/NIDDK) [E]
YesYesNo4/4/2014 9:48 AM
The invention is directed to an adenoviral vector comprising (a) at least one insertion site for cloning a heterologous gene, and, in an orientation opposite to the direction of transcription of the adenoviral region into which it is inserted, (b) a heterologous promoter positioned upstream from the insertion site, (c) a eukaryotic splice acceptor and splice donor site positioned between the promoter and the insertion site; and (d) a polyadenylation sequence positioned downstream of the insertion site. The invention also provides a host cell infected with such a vector, a method of producing a selected protein, and a method of delivering a heterologous gene to an animal heart.
Research Materials356
  
http://www.google.com/patents/US20090247473
Appella, Daniel (NIH/NIDDK) [E]
YesYesYes4/4/2014 9:48 AM
These inventions provide the compositions, pharmaceutical carrier, and usages of the new Acylthiols (E-329-2000 family) and Thioether pro-drug (E-177-2010 family) compounds in treatment of retroviral infections such as HIV. These compounds target the highly-conserved nucleocapsid protein 7 (NCp7) of HIV-1. This protein functions throughout the viral replication cycle and is involved with reverse transcription, integration, and assembly and packaging of the viral genomic material.  This protein is conserved among strains of HIV-1. Activity of these compounds against the nucleocapsid protein leads to inactivation of the virus via disruption of the zinc fingers, integral for infectivity, without significantly affecting cellular proteins.
 
These compounds can be prepared from inexpensive starting materials and two “one-pot” reactions. Thus, they open the possibility for an effective drug treatment for HIV that could reach underdeveloped countries. These new compounds have the potential to be used both as a systemic drug for the treatment of HIV-1 infection and as a topically-applied or controlled-release barrier to prevent viral transmission.
Research Materials353
  
https://www.google.com/patents/WO2012116254A2
Bewley, Carole (NIH/NIDDK) [E]
YesYesYes4/4/2014 9:47 AM

This invention, offered for licensing and commercial development, relates to a new class of naturally occurring antimicrobial compounds called Chrysophaetins, and to their synthetic analogues. Isolated from an alga species, the mechanism of action of these compounds is through the inhibition of bacterial cytoskeletal protein FtsZ, an enzyme necessary for the replication of bacteria. FtsZ is responsible for Z-ring assembly in bacteria, which leads to bacterial cell division. Highly conserved among all bacteria, FtsZ is a very attractive antimicrobial target.

 
The chrysophaetin exhibits antimicrobial activity against drug resistant bacteria, methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant Enterococcus faecalis (VRE), as well as other drug susceptible strains.
Research Materials348
  
https://www.google.com/patents/WO2009126308A2
Shiloach, Joseph (NIH/NIDDK) [E]
YesYesNo4/4/2014 9:45 AM

The present invention features methods of producing immunogenic compositions and viruses, methods of treating and preventing viral infection, and methods of producing an immune response using cells that express a polypeptide selected from the group consisting of: cdkl3, siat7e, Iama4, cox15, egr1, gas6, map3k9, and gap43, and a virus.

Research Materials313
  
http://patft.uspto.gov/netacgi/nph-Parser?Sect1=PTO2&Sect2=HITOFF&p=1&u=%2Fnetahtml%2FPTO%2Fsearch-bool.html&r=1&f=G&l=50&co1=AND&d=PTXT&s1=Germino.INNM.&OS=IN/Germino&RS=IN/Germino
Germino, Gregory (NIH/NIDDK) [E]
YesYesNo4/4/2014 9:38 AM

Compositions useful for examining the PKD1 gene are provided. In addition, methods for detecting mutations of the PKD1 gene, which can be associated with autosomal dominant polycystic kidney disease in humans, are provided. Methods for diagnosing a mutant PKD1 gene sequence in a subject also are provided, as are methods of treating a subject having a PKD1-associated disorder.

Research Materials326
  
http://patft.uspto.gov/netacgi/nph-Parser?Sect1=PTO2&Sect2=HITOFF&u=%2Fnetahtml%2FPTO%2Fsearch-adv.htm&r=1&f=G&l=50&d=PTXT&p=1&S1=7316903&OS=7316903&RS=7316903
Mizuuchi, Kiyoshi (NIH/NIDDK) [E]
YesYesNo4/4/2014 9:38 AM

The present invention relates, e.g., to a method of detecting a mismatch in a double stranded nucleic acid target, comprising (a) contacting the target with (i) a Mu-end nucleic acid, and (ii) a phage Mu transposase, under conditions effective for the Mu-end nucleic acid to transpose into the target at about the site of a mismatch, if the target comprises a mismatch, and (b) detecting transposition of the Mu-end DNA into the target, wherein transposition of the Mu-end nucleic acid into the target at a predominant site indicates the presence of a mismatch at that site.

Research Materials316
  
Epibatidine and derivatives, compositions and methods of treating pain
Garraffo, Hugo (NIH/NIDDK) [E]
YesYesNo4/4/2014 9:38 AM
The present invention is directed to compounds, compositions and methods of treating pain, and derivatives that have potent analgetic activity. The compounds have the formula: ##STR1## wherein R.sup.1 is selected from H, lower alkyl, C.sub.3 -C.sub.9 cycloalkyl, acyl, and C.sub.3 -C.sub.9 cycloalkylalkyl, haloalkyl, alkenyl, alkynyl, hydroxyalkyl, or C.sub.3 -C.sub.8 cycloalkenyl or C.sub.3 -C.sub.8 cycloalkynyl; and wherein R is selected from cycloalkyl, aryl, heteroaryls (selected from the group consisting of pyridyl, thienyl, furanyl, imidazolyl, pyrazinyl, and pyrimidyl) or phenoxy and wherein said R groups can be substituted with hydroxyl, C.sub.1 -C.sub.6 lower alkyl, C.sub.2 -C.sub.6 alkenyl, C.sub.1 -C.sub.6 lower alkoxyl, halo, C.sub.1 -C.sub.6 haloalkyl, amino, C.sub.1 -C.sub.6 alkylamino and C.sub.2 -C.sub.10 dialkylamino, and sulfonamido or a pharmaceutically acceptable salt thereof.
Research Materials315
  
http://patft.uspto.gov/netacgi/nph-Parser?Sect1=PTO2&Sect2=HITOFF&u=%2Fnetahtml%2FPTO%2Fsearch-adv.htm&r=1&f=G&l=50&d=PTXT&p=1&S1=7557196&OS=7557196&RS=7557196
Rodgers, Griffin (NIH/NIDDK) [E]
YesYesNo4/4/2014 9:33 AM

An isolated acid having the sequence of a) SEQ ID NO: 1; b) the sequence of SEQ ID NO: 2; c) the sequence of SEQ ID NO: 3; d) a sequence complementary to any of a), b), or c); or e) a sequence of at least 10 contiguous nucleotides specific for any of a)-d). The invention relates to the identification and characterization of a hitherto unidentified human gene, hGC-1. The protein encoded by hGC-1 appears to be a member of the olfactomedin-related proteins. The invention relates generally to the gene (hGC-1), nucleic acids, cDNA, vectors, polypeptides, protein, antibodies, cells, transgenic animal, and other compositions related to hGC-1. Additionally, primers are provided for identifying hGC-1. The invention further relates to methods of using these compositions, such as diagnosis and treatment of various cancers, and kits comprising these compositions.

Research Materials319
  
http://patft.uspto.gov/netacgi/nph-Parser?Sect1=PTO2&Sect2=HITOFF&u=%2Fnetahtml%2FPTO%2Fsearch-adv.htm&r=1&f=G&l=50&d=PTXT&p=1&S1=5637488&OS=5637488&RS=5637488
Louis, John (NIH/NIDDK) [E]
YesYesNo4/4/2014 9:32 AM

The invention is a synthetic DNA sequence for encoding a specific enzyme or protease. The protease is essential for the completion (replication) of an infective human immunodeficiency virus (HIV). The invented gene is desirable for the expression of the protease by recombinant methodology in prokaryotic and/or eukaryotic cells and the production of a commercially desirable amount of the protease for biochemical and physical characterization, necessary to find effective inhibitor of the protease, and thereby to block the production of infectious human immunodeficiency virus (HIVs).

Research Materials344
  
http://www.google.com/patents/WO2011127388A2
Gershengorn, Marvin (NIH/NIDDK) [E]
Neumann, Susanne (NIH/NIDDK) [E]
YesYesNo4/4/2014 9:32 AM

TSHR inverse agonists and neutral antagonists that are useful for treating Graves' orbitopathy, Graves' hyperthyroidism and/or thyroid cancer.

Research Materials332
  
http://patft.uspto.gov/netacgi/nph-Parser?Sect1=PTO2&Sect2=HITOFF&p=1&u=%2Fnetahtml%2FPTO%2Fsearch-bool.html&r=1&f=G&l=50&co1=AND&d=PTXT&s1=%22Linking+compounds+useful+coupling+carbohydrates+amine-containing+carriers%22&OS=
Kovac, Pavol (NIH/NIDDK) [E]
YesYesNo4/4/2014 9:31 AM

The present invention provides a method to couple a glycosyl donor to an amine-containing carrier or substrate material using as a spacer a compound of the general formula I: ##STR1## in which n and m are each independently an integer of from 1 to 12, R.sub.1 and R.sub.2 are each independently H, lower alkyl, a hydroxyl group, or a substituent which does not interfere with the linking reactions, R.sub.4 and R.sub.5 are each independently H, lower alkyl, a hydroxyl group, or a substituent which does not interfere with the linking reactions, R.sub.3 and R'.sub.3 are each independently an optionally substituted lower alkyl or R.sub.3 and R'.sub.3 can be joined to form an optionally substituted cyclic moiety having from 2 to 5 carbon atoms.

Research Materials343
  
http://www.google.com/patents/WO2010047674A1
Gershengorn, Marvin (NIH/NIDDK) [E]
Neumann, Susanne (NIH/NIDDK) [E]
YesYesNo4/4/2014 9:31 AM

NIH investigators have discovered a series of low molecular weight thyroid-stimulating hormone (TSH) receptor modulators for use in the procedure to detect residual thyroid cancer cells following thyroidectomy. As small molecules, these compounds are orally available and are expected to be less costly and more straightforward to produce than recombinant protein counterparts currently on the market.  These compounds appear be orally available, would be less difficult and expensive to produce, and are also more potent and/or specific for the TSH receptor than other known small-molecule TSH receptor agonists. In addition to use in thyroid cancer screening, these compounds may also be useful for adjunctive treatment (with radioactive iodide) of thyroid cancer, and certain forms of hypothyroidism.

 

Disclosed are oxo-hydroquinazolines of formula I that are useful as selective TSHR agonists. The compounds may be used for detecting or treating thyroid cancer, or treating a bone degenerative disorder.

Research Materials335
  
http://patft.uspto.gov/netacgi/nph-Parser?Sect1=PTO2&Sect2=HITOFF&p=1&u=%2Fnetahtml%2FPTO%2Fsearch-bool.html&r=1&f=G&l=50&co1=AND&d=PTXT&s1=%22MEN1,+gene+associated+multiple+endocrine+neoplasia+type+1,+menin+polypeptides+uses+%22&OS=
Agarwal, Sunita (NIH/NIDDK) [E]
YesYesNo4/4/2014 9:30 AM
The invention relates to the discovery of a novel tumor suppressor gene which is associated with multiple endocrine neoplasia type 1. The gene has been designated MEN1 and the gene product is menin. The absence of this protein and associated mutations in the corresponding gene have been identified in individuals suffering from multiple endocrine neoplasia type 1. The identification of this marker for multiple endocrine neoplasia type 1 has diagnostic uses as well as for gene therapy.
Research Materials321
  
http://patft.uspto.gov/netacgi/nph-Parser?Sect1=PTO2&Sect2=HITOFF&u=%2Fnetahtml%2FPTO%2Fsearch-adv.htm&r=4&f=G&l=50&d=PTXT&p=1&S1=6,077,694&OS=6,077,694&RS=6,077,694
Louis, John (NIH/NIDDK) [E]
YesYesNo4/4/2014 9:30 AM

​The present invention provides expression systems for exogenous polypeptides wherein the polypeptide is expressed as a fusion protein together with clover yellow virus Nuclear Inclusion a (NIa), the NIa component serving to autolyze the fusion protein after expression. This system can be used to express a novel polypeptide which we have designated KM31-7 protein and which is capable of reducing dichloroindophenol and reduced glutathione. This polypeptide is useful in the treatment of disorders caused by oxidative stress.​

Research Materials336
  
Method of detecting antigenic, nucleic acid-containing macromolecular entities
Liang, Jake (NIH/NIDDK) [E]
YesYesNo4/4/2014 9:29 AM
A method for the detection of nucleic acid-containing moieties is described which combines affinity capture of the moiety with detection and identification of the moiety's nucleic acid.
Research Materials333
  
http://patft.uspto.gov/netacgi/nph-Parser?Sect1=PTO2&Sect2=HITOFF&p=1&u=%2Fnetahtml%2FPTO%2Fsearch-bool.html&r=10&f=G&l=50&co1=AND&d=PTXT&s1=%22Method+targeting+DNA%22&OS="Method+targeting+DNA"&RS="Method+targeting+DNA"
Hsieh, Peggy (NIH/NIDDK) [E]
YesYesNo4/4/2014 9:28 AM

The present invention relates to a method of forming a three-stranded DNA molecule wherein each strand of the three-stranded DNA molecule is hybridized (that is, non-covalently bound) to at least one other strand of the three-stranded DNA molecule. The method comprises:

  • Contacting a recombination protein with a double-stranded DNA molecule and with a single-stranded DNA molecule sufficiently complementary to one strand of the double-stranded DNA molecule to hybridize therewith, which contacting is effected under conditions such that the single-stranded DNA molecule hybridizes to the double-stranded molecule so that the three stranded DNA molecule is formed.
Research Materials339
  
http://www.google.com/patents/WO1998025598A2
Mueller, Elisabetta (NIH/NIDDK) [E]
YesYesNo4/4/2014 9:27 AM

Methods for inhibiting proliferation of a PPARη-responsive hyperproliferative cell using PPARη agonists are described. Pharmaceutical compositions as well as methods for diagnosing and treating a PPARη-responsive hyperproliferative cell are also described.

Research Materials317
  
http://patft.uspto.gov/netacgi/nph-Parser?Sect1=PTO2&Sect2=HITOFF&u=%2Fnetahtml%2FPTO%2Fsearch-adv.htm&r=3&f=G&l=50&d=PTXT&p=1&S1=6974698&OS=6974698&RS=6974698
Miller, Jeff (NIH/NIDDK) [E]
YesYesNo4/4/2014 9:27 AM

Methods for delivering a biologically active molecule into a cell by linking a molecule to the cell surface, wherein the molecule can act as a surface receptor, then complexing the biologically active molecule with a ligand for the surface receptor, and finally contacting the biologically active molecule-ligand complex with the cell surface are disclosed. Delivery of any biologically active molecule, e.g. proteins, enzymes, nucleic acids, hormones, nucleic acids, and oligonucleotides, is contemplated. The use of biotin or biotinylated antibodies as the surface receptor is disclosed. The use of PEI and PEI-avidin conjugates complexed with oligonucleotides for delivery into a directly or indirectly biotinylated cell surface, along with the PEI-avidin-nucleic acid compositions, are disclosed. Primary and cultured cells with a covalently linked surface receptor molecule, such as biotin, on their surfaces are also disclosed.

Research Materials323
  
http://patft.uspto.gov/netacgi/nph-Parser?Sect1=PTO2&Sect2=HITOFF&u=%2Fnetahtml%2FPTO%2Fsearch-adv.htm&r=2&f=G&l=50&d=PTXT&p=1&S1=7,763,451&OS=7,763,451&RS=7,763,451
Shiloach, Joseph (NIH/NIDDK) [E]
YesYesNo4/4/2014 9:27 AM

The invention relates to improved methods of producing and recovering B. anthracis protective antigen (PA), especially modified PA which is protease resistant, and to methods of using of these PAs or nucleic acids encoding these PAs for eliciting an immunogenic response in humans, including responses which provide protection against, or reduce the severity of, B. anthracis bacterial infections and which are useful to prevent and/or treat illnesses caused by B. anthracis, such as inhalation anthrax, cutaneous anthrax and gastrointestinal anthrax.

Research Materials329
  
http://patft.uspto.gov/netacgi/nph-Parser?Sect1=PTO2&Sect2=HITOFF&p=1&u=%2Fnetahtml%2FPTO%2Fsearch-bool.html&r=1&f=G&l=50&co1=AND&d=PTXT&s1=%22Methods+identifying+negative+antagonists+G+protein+coupled+receptors%22&OS=
Gershengorn, Marvin (NIH/NIDDK) [E]
YesYesNo4/4/2014 9:26 AM

The present invention is directed to a constitutively active G protein coupled receptor of human herpesvirus 8, as well as a method of identifying negative antagonists of a constitutively active G protein coupled receptor. The method comprises co-expressing in a host cell a constitutively active G protein coupled receptor and a reporter protein, wherein expression of the reporter protein is controlled by a promoter responsive to a signalling pathway activated by the constitutively active G protein coupled receptor; exposing the host cell to a test substance; and determining a level of reporter protein activity, wherein the level of reporter protein activity indicates effectiveness of the test substance as a negative antagonist of the constitutively active G protein coupled receptor. The invention further provides a method of preventing tumor formation or cell proliferation caused by a constitutively active G protein coupled receptor. This method comprises administering an amount of the negative antagonist so identified to a subject in an amount effective to prevent tumor formation or cell proliferation.

Research Materials330
  
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Gershengorn, Marvin (NIH/NIDDK) [E]
YesYesNo4/4/2014 9:26 AM

The present invention is directed to a strategy to discover small peptides that will activate any G protein coupled receptor (GPCR) or inactivate any constitutively active GPCR. The strategy uses combinatorial peptide libraries to screen millions of random peptides for agonist/negative antagonist activity. The method of the subject invention comprises expressing a peptide of a peptide library tethered to a G protein coupled receptor of interest in a cell, and monitoring the cell to determine whether the peptide is an agonist or negative antagonist of the GPCR of interest. The peptide is tethered to the GPCR by replacing the amino terminus of the GPCR with the amino terminus of a self-activating receptor, and replacing the natural peptide ligand present in the amino terminus of the self-activating receptor with the peptide of the peptide library. In one embodiment for discovery of agonists, a ligand of the self-activating receptor is used to cleave the resulting amino terminus to expose the peptide of the peptide library. In another embodiment for discovery of agonists or negative antagonists, the GPCR construct ends at the peptide so the peptide is always exposed. Preferably, the self-activating receptor is the thrombin receptor and the ligand of the self-activating receptor is thrombin.

Research Materials337
  
http://patft.uspto.gov/netacgi/nph-Parser?Sect1=PTO2&Sect2=HITOFF&p=1&u=%2Fnetahtml%2FPTO%2Fsearch-bool.html&r=3&f=G&l=50&co1=AND&d=PTXT&s1=5610050&OS=5610050&RS=5610050
Liang, Jake (NIH/NIDDK) [E]
YesYesNo4/4/2014 9:26 AM

The invention relates to methods and compositions for inhibition of viral replication. In particular, termination of replication of hepatitis B virus is achieved by introducing into a target cell an antisense oligonucleotide having a sequence substantially complementary to an mRNA which is in turn complementary to a portion of the minus strand of a hepatitis viral genome, which portion encoding solely part or all of the terminal protein region of the viral polymerase.

Research Materials325
  
http://patft.uspto.gov/netacgi/nph-Parser?Sect1=PTO2&Sect2=HITOFF&u=%2Fnetahtml%2FPTO%2Fsearch-adv.htm&r=11&f=G&l=50&d=PTXT&p=1&S1=4,716,105&OS=4,716,105&RS=4,716,105
Mizuuchi, Kiyoshi (NIH/NIDDK) [E]
YesYesNo4/4/2014 9:26 AM
The present invention discloses a rapid method of sequencing a relatively large segment of deoxyribonucleic acid. The method in part comprises high frequency insertion of a suitable transposon into a segment of DNA of interest. Preferable use of Mu transposons is described. A plasmid having mini-Mu transposons has been prepared and disclosed.
Research Materials349
  
http://www.ott.nih.gov/Technologies/abstractDetails.aspx?RefNo=2486
Abd-elmoniem, Khaled (NIH/NIDDK) [E]
YesYesYes4/4/2014 9:25 AM

Atherosclerosis is the underlying cause of coronary artery disease, the number one cause of death in the United States.  It is a slowly progressing chronic disease in which cholesterol deposition, invasion of monocytes and smooth muscle cells, and inflammation lead to the formation of atherosclerotic plaques in the intima of the coronary artery wall that progressively thicken it.  Atherosclerosis begins in young people, who remain asymptomatic for many years, but are at increased risk of having a heart attack.  Myocardial infarction occurs when insufficient blood supplies the heart muscle because atherosclerotic enlargement of the coronary artery wall has narrowed its lumen by >50% or, more commonly, when the integrity of the fibrous cap of a vulnerable plaque is fractured triggering thrombosis that occludes the artery.

 

The present invention provides a technology that can identify atherosclerosis in coronary arteries at an early stage while an individual at high risk for cardiovascular disease is still asymptomatic so that preventive measures can be instituted.  It uses MR Imaging systems that can image small-diameter vessels like coronary arteries and algorithms that use these data to calculate the thickness of the vessel wall, an early indicator of atherosclerosis.  By using an inversion radiofrequency pulse triggered by a signal connected to the cardiac cycle, image resolution is not compromised by cardiac motion, so that multiple time-resolved images of an orthogonal slice of the region of interest can be obtained for more accurate results. 

 

Unlike alternative approaches, the present technology measures an early marker of atherosclerosis in asymptomatic patients, is not invasive, and does involve exposure to ionizing radiation or contrast dyes.  It should be useful in evaluating whether a therapeutic strategy is effective in the short term and in reducing long-term cardiovascular events, and in deciding whether treatment should be instituted in high-risk, asymptomatic patients.

Research Materials342
  
http://www.google.com/patents/WO2011116282A3
Garraffo, Hugo (NIH/NIDDK) [E]
YesYesNo4/4/2014 9:25 AM

The invention provides novel nicotinic acetylcholine receptor agonists, for example, phaiitasmidine and derivatives thereof, for example a compound of formula (I). Also disclosed are methods of treating disorders responsive to nicotinic acetylcholine receptor agonists such as Alzheimer's disease, schizophrenia, Myasthenia Gravis, Tourette's syndrome, Parkinson's disease, epilepsy, pain, and cognitive dysfunction by treatment with the nicotinic acet lcholine rece tor a onists.

Research Materials345
  
https://www.google.com/patents/WO2013009826A9
Kovac, Pavol (NIH/NIDDK) [E]
YesYesYes4/4/2014 9:25 AM

A new conjugate vaccine for cholera has been developed. The invention includes a new method to conjugate the O-specific polysaccharide-core part of the bacterial lipopolysaccharide and protein subcomponents. Conventional technology has entailed chemical treatment of both components to introduce linkers, which made them amenable for covalent linking. The new method simplifies production by utilizing squaric acid chemistry for conjugating the free amine-containing species (e.g. polysaccharides) directly to amine-containing species (e.g. proteins) without prior modification of either component. While demonstrated in this new cholera prototype vaccine, the technology is envisioned as generally applicable, thereby streamlining a complex production process.

Research Materials341
  
http://www.google.com/patents/US20100047785
Germino, Gregory (NIH/NIDDK) [E]
YesYesNo4/4/2014 9:24 AM

The present invention relates to methods of detecting novel mutations in a PKD1 and/or PKD2 gene that have been determined to be associated with autosomal dominant polycystic kidney disease (ADPKD) in order to detect or predict the occurrence of ADPKD in an individual.

Research Materials354
  
https://www.google.com/patents/US20120322053
Appella, Daniel (NIH/NIDDK) [E]
YesYesYes4/4/2014 9:24 AM

The laboratory of Daniel Appella, PhD. has developed a prototype HIV testing kit that employs a peptide nucleic acid probe to capture HIV RNA recovered from patient blood.  The probe targets a highly conserved segment of the Gag sequence.   Initial data from tests run side by side with PCR show high sensitivity and specificity.  The test, excluding the cost for an RNA extraction kit, has been calculated to be under $0.70 per sample based on retail price lists for reagents. This is within the cost target suggested by the World Health Organization.  It is hoped that the test would be suitable for use in a developing country.  While the test has not been optimized, operated as is, the assay would take 3-4 hours providing results while a patient is still at the clinic.

Research Materials310
  
http://patft.uspto.gov/netacgi/nph-Parser?Sect1=PTO2&Sect2=HITOFF&p=1&u=%2Fnetahtml%2FPTO%2Fsearch-bool.html&r=37&f=G&l=50&co1=AND&d=PTXT&s1=%22Polycystic+kidney+disease+gene%22&OS=%22Polycystic+kidney+disease+gene%22&RS=%22Polycystic+kidney+disease+gene%
Germino, Gregory (NIH/NIDDK) [E]
YesYesNo4/4/2014 9:23 AM

The present invention involves isolated nucleic acid encoding human PKD1, and sequences derived therefrom. The invention also encompasses vectors comprising these nucleic acids, host cells transformed with the vectors, and methods for producing PKD1 protein or fragments thereof. In another aspect, the invention involves isolated oligonucleotides that hybridize only to the authentic expressed PKD1 gene, and not to PKD1 homologues. In yet another aspect, the invention involves isolated mutant PKD1 genes, and their cDNA cognates. Further provided are isolated oligonucleotides that discriminate between normal and mutant versions of the PKD1 gene. Methods and compositions for treating APKD or disease conditions having the characteristics of APKD are also provided.

Research Materials311
  
http://patft.uspto.gov/netacgi/nph-Parser?Sect1=PTO2&Sect2=HITOFF&p=1&u=%2Fnetahtml%2FPTO%2Fsearch-bool.html&r=3&f=G&l=50&co1=AND&d=PTXT&s1=germino.INNM.&OS=IN/germino&RS=IN/germino
Germino, Gregory (NIH/NIDDK) [E]
YesYesNo4/4/2014 9:23 AM

The present invention involves isolated nucleic acid encoding human PKD1, and sequences derived therefrom. The invention also encompasses vectors comprising these nucleic acids, host cells transformed with the vectors, and methods for producing PKD1 protein or fragments thereof. In another aspect, the invention involves isolated oligonucleotides that hybridize only to the authentic expressed PKD1 gene, and not to PKD1 homologues. In yet another aspect, the invention involves isolated mutant PKD1 genes, and their cDNA cognates. Further provided are isolated oligonucleotides that discriminate between normal and mutant versions of the PKD1 gene. Methods and compositions for treating APKD or disease conditions having the characteristics of APKD are also provided.

Research Materials355
  
http://www.google.com/patents/EP2569328A2?cl=en
Appella, Daniel (NIH/NIDDK) [E]
YesYesYes4/4/2014 9:23 AM

The invention concerns compositions comprising strands of polynucleotide and strands of PNA, each PNA strand comprising:

  • (i) from 2 to 50 nucleobase subunits and
  • (ii) one or more gamma substituents.

The PNA strands are complementary to at least a portion of at least some of the polynucleotide strands, and the molar ratio of PNA strands to polynucleotide strands being at least 1:1. Certain gamma substituents are capable of effecting attachment of a PNA strand to a cell. The invention also concerns construction of nanostructure platforms and vaccines and use of the inventive compositions in inhibiting disease states in mammals.

Research Materials314
  
http://patft.uspto.gov/netacgi/nph-Parser?Sect1=PTO2&Sect2=HITOFF&u=%2Fnetahtml%2FPTO%2Fsearch-adv.htm&r=3&f=G&l=50&d=PTXT&p=1&S1=6,322,981&OS=6,322,981&RS=6,322,981
Rodgers, Griffin (NIH/NIDDK) [E]
YesYesNo4/4/2014 9:21 AM

The present invention relates to the simultaneous and specific identification of the variant forms of α-thalassemia. This invention utilizes simple and readily available equipment to rapidly identify, diagnose and differentiate the different forms of α-thalassemia. Specifically, the present invention relates to a simple and rapid non-radioisotopic technique for the diagnosis and differentiation of the common forms of α-thalassemia has been developed. This approach works on any biological tissue including blood, wherein the assay works equally well with fresh blood and dried blood samples stored on filter paper.

Research Materials308
  
http://patft.uspto.gov/netacgi/nph-Parser?Sect1=PTO2&Sect2=HITOFF&u=%2Fnetahtml%2FPTO%2Fsearch-adv.htm&r=6&f=G&l=50&d=PTXT&p=1&S1=5281519&OS=5281519&RS=5281519
Schechter, Alan N (NIH/NIDDK) [E]
Rodgers, Griffin (NIH/NIDDK) [E]
YesYesNo4/4/2014 9:20 AM

A simple, rapid and reliable method for diagnosis of thalassemia is described. The method comprises amplification of the cDNA by polymerase chain reaction and determining the ratio between α and β hemoglobin chain mRNAs.

Research Materials302
  
Mutant Mouse:  Sphk1 (Sphingosine kinase 1)Animal ModelsDevelopmental Biologyhttp://www.ncbi.nlm.nih.gov/pubmed/17346996
Proia, Richard (NIH/NIDDK) [E]
YesYesYes4/4/2014 8:34 AM

A Sphingosine kinase 1 (Sphk1) knockout mouse

 

Sphingosine kinase 1 and 2 are enzymes that produce sphingosine-1-phosphate (S1P), a potent bioactive compound that activates a family of G-protein coupled receptors known as S1P receptors.  Triggering these receptors on cells has important effects related to inflammation, immunity, cancer, angiogenesis, cell proliferation, adhesion, cardiovascular function, nervous system function and injury responses.  Sphingosine kinase 1 is the predominant isozyme for extracellular S1P production.  Sphingosine kinase 2 is the predominant isozyme that activates Fingolimod (brand name: Gilenya™), an immunomodulating drug that has been approved by the FDA for treating multiple sclerosis. The sphingosine kinase 1 knockout mouse and the sphingosine kinase 2 knockout mouse will be valuable for determining the functions of sphingosine-1- phosphate and S1P receptors.  These mice will also be useful for the study of Fingolimod and related compounds.

Research Materials298
  
Mutant Mouse:  Stat1Animal ModelsImmunology and Inflammationhttp://www.ncbi.nlm.nih.gov/pubmed/21076615
Hennighausen, Lothar Dr. (NIH/NIDDK) [E]
YesYesYes4/4/2014 8:34 AM

Selective inactivation of Stat 1 in mammary cells indicates that its effect as a tumor suppressor in breast is direct.

 

STAT1 is considered a tumor suppressor, but it is not known if this effect occurs directly in mammary cells or secondarily by disrupting interferon signaling through the JAK/STAT1 pathway to induce immune responses.  ERBB2/neu-induced breast cancer appeared sooner in mice lacking STAT1 only in mammary cells than in wild-type mice, indicating that STAT1 tumor suppression was intrinsic to mammary cells and not secondary to an induced immune response.

Research Materials293
  
Mutant Mouse: Stat 5a (Signal transducer and activator of transcription)Animal ModelsDevelopmental Biologyhttp://www.ncbi.nlm.nih.gov/pubmed/9009201
Hennighausen, Lothar Dr. (NIH/NIDDK) [E]
YesYesYes4/4/2014 8:33 AM

Stat 5a Knockout: Stat5a deficiency results in the loss of prolactin-dependent mammary gland development and lactogenesis.

 

Prolactin induces mammary gland development and lactogenesis.  Binding of Prolactin to its receptor leads to the phosphorylation and activation of STAT (signal transducers and activators of transcription) proteins.  Two Stat proteins, Stat 5a and Stat5b, are expressed in mammary tissues during pregnancy.  Stat5a null mice developed normally, and were indistinguishable from hemizygous and wild-type littermates in size, weight and fertility.  Mammary lobulo-alveolar outgrowth during pregnancy was reduced and females failed to lactate after parturition.  Stat5b, despite 96% similarity to Stat5a, could not compensate for the loss of Stat5a.  Stat5a is the principal and obligate mediator of mammopoietic and lactogenic signaling.

Research Materials295
  
Mutant Mouse: Stat5a/bHematologic DiseaseAnimal ModelsDevelopmental Biologyhttp://www.ncbi.nlm.nih.gov/pubmed/15340066
Hennighausen, Lothar Dr. (NIH/NIDDK) [E]
YesYesYes4/4/2014 8:33 AM

Conditional knockout of Stat5a and Stat5b: Combined deletion of conserved Stat5a and Stat5b in mammary epithelium at different times during pregnancy reveal multiple distinct functions.

 

The signal transducer and activator of transcription (STAT) family of transcription factors conveys signals from membrane receptors to the nucleus, where they activate diverse genetic programs.  Stat5a and Stat5b are highly conserved proteins that are activated by many cytokines, erythropoietin, prolactin and growth hormone.  Despite their similarities, they have many unique functions.  Stat5a deficiency results in the loss of prolactin-dependent mammary gland development, but does not affect body growth.  Inactivation of Stat5b does not adversely affect mammary development and function, but leads to severe growth retardation.  To study the effects of combined deficiency of Stat 5a and 5b before and during pregnancy, loxP was added to the ends of a DNA fragment that contains the two genes which are located within a stretch of 110 kb on chromosome 11 in a head to head orientation with no other genes between them. The loxP-flanked fragment was introduced into the genome using homologous recombination, and deleted using two transgenic lines expressing Cre in mammary epithelium at different times.  Deletion of Stat 5 before pregnancy prevents epithelial proliferation. Ductal characteristics are retained but differentiation into secretory alveoli does not occur.  When deletion of Stat5 occurs late in pregnancy after differentiation has started, differentiation is halted and premature death occurs.

Research Materials297
  
Mutant Mouse:  WAP-Cre (whey acidic protein promoter directs Cre recombinase)Animal ModelsDevelopmental Biologyhttp://www.ncbi.nlm.nih.gov/pmc/articles/PMC147032/
Hennighausen, Lothar Dr. (NIH/NIDDK) [E]
YesYesYes4/4/2014 8:32 AM

Cre-recombinase under the control of the whey acidic acid protein was only detected in alveolar epithelial epithelial cells of mammary tissue during lactation, and transcription occurred at all stages of mammary development.

 

The Cre recombinase from bacteriophage P1 excises intervening DNA sequences located between two unidirectional lox sites positioned on the same linear DNA segment, leaving one lox site behind.  Through insertion of lox sites via homologous recombination into the gene of interest and targeting Cre recombinase expression to a specific cell type using a tissue-specific promoter, it is possible to introduce predetermined deletions into the mammalian genome.  To delete genes specifically from mammary gland, transgenic mice were created carrying the Cre gene under the control of the whey acidic protein (WAP) gene promoter.  Expression of WAP-Cre was only detected in alveolar epithelial cells of mammary tissue during lactation.  Recombination mediated by Cre under control of the WAP gene promoter was largely restricted to the mammary gland but occasionally was observed in the brain.  High-level transcriptional activity of WAP-based transgenes can be obtained at every stage of mammary development.

Research Materials296
  
Mutant Mouse: MMTV-Cre (Mammary tumor virus long terminal repeat-Cre recombinase)Hematologic DiseaseAnimal ModelsDevelopmental Biologyhttp://www.ncbi.nlm.nih.gov/pmc/articles/PMC147032/
Hennighausen, Lothar Dr. (NIH/NIDDK) [E]
YesYesYes4/4/2014 8:32 AM

Cre-recombinase under the control of mouse mammary tumor virus long terminal repeat (MMTV) was expressed in the salivary gland and mammary epithelial cells of adult mice, and induced recombination in all tissues.

 

The Cre recombinase from bacteriophage P1 excises intervening DNA sequences located between two unidirectional lox sites positioned on the same linear DNA segment, leaving one lox site behind.  Through insertion of lox sites via homologous recombination into the gene of interest and targeting Cre recombinase expression to a specific cell type using a tissue-specific promoter, it is possible to introduce predetermined deletions into the mammalian genome.  To delete genes specifically from mammary gland, transgenic mice were created carrying the Cre gene under the control of the mouse mammary tumor virus (MMTV) long terminal repeat (LTR).  In adult MMTV-Cre mice, expression of the transgene was confined to striated ductal cells of the salivary gland and mammary epithelial cells in virgin and lactating mice.  In contrast to WAP-Cre, however, Cre expression under control of the MMTV LR resulted in recombination in all tissues.

Research Materials290
  
Mutant Mouse:  Kdm6a (lysine (K)-specific demethylase 6A)Animal Models; Cell LinesDevelopmental Biology
Ge, Kai (NIH/NIDDK) [E]
YesYesYes4/4/2014 8:31 AM

UTX-flox.  Conditional knockout mice for the histone demethylase UTX (Kdm6a) conditional knockout will help understand its role as a tumor suppressor.

 

Di- and tri-methylations on histone H3 lysine 27 (H3K27me2 and H3K27me3) are epigenetic marks for gene repression. UTX (ubiquitously transcribed X chromosome protein), also known as Kdm6a (lysine (K)-specific demethylase 6a) is a histone demethylase that specifically removes H3K27me2 and H3K27me3.  UTX knockout mice are embryonic lethal, so we have generated UTX conditional knockout mice (UTX-flox) in which exon 24 is flanked with loxP sites. UTX has been found to be a tumor suppressor gene mutated in a wide variety of human cancers. The UTX-flox mice provide a valuable tool to study how UTX functions as a tumor suppressor and as an epigenetic regulator of gene expression.

Research Materials309
  
Minton, Allen P (NIH/NIDDK) [E]
YesYesYes4/4/2014 8:30 AM

NIDDK scientists have developed a capillary-based device and system for measuring the rheological properties of solutions of synthetic and biological polymers. The device automatically serially dilutes and varies the flow rate of a sample, permitting measurement of solution viscosity across wide ranges of concentration and shear rate without changing samples. Viscosity is calculated directly from Poiseuille’s law, given the measured difference in pressure between two ends of a capillary tube through which the solution is flowing at a known rate. The device can rapidly and accurately assay solute stability, solute-solvent and solute-solute interactions in solutions of proteins and other macromolecules of biotechnological and pharmaceutical interest, as well as solution injectability.

Research Materials318
  
Hanover, John (NIH/NIDDK) [E]
Love, Dona (NIH/NIDDK) [E]
YesYesNo4/4/2014 8:30 AM

Collaboration on the development of a transgenic model of tau pathology and tau-mediated neurodegeneration.  Each party contributed a mouse model which were crossed.  The resulting offspring underwent biochemical and immunohistochemical measurement of tau pathology and neurodegeneration, together with behavioural and/or locomotor testing of function.

Research Materials312
  
http://patft.uspto.gov/netacgi/nph-Parser?Sect1=PTO2&Sect2=HITOFF&p=1&u=%2Fnetahtml%2FPTO%2Fsearch-bool.html&r=37&f=G&l=50&co1=AND&d=PTXT&s1=%22Polycystic+kidney+disease+gene%22&OS=%22Polycystic+kidney+disease+gene%22&RS=%22Polycystic+kidney+disease+gene%
Germino, Gregory (NIH/NIDDK) [E]
YesYesNo4/4/2014 8:29 AM

The present invention provides methods and compositions for treating cyst formation in PKD1-associated epithelial cells. Such methods encompass administering an isolated human PKD1 gene, or fragments of the gene, under conditions that result in expression of therapeutically effective amounts of all, or part of, the PKD1 protein. The invention also encompasses compositions for treating cyst formation associated with APKD.

Research Materials284
  
Podocin/rtTA DNA transgeneAnimal ModelsDevelopmental Biologyhttp://jasn.asnjournals.org/content/14/8/1998.short
Kopp, Jeffrey, Dr. (NIH/NIDDK) [E]
YesYesYes4/4/2014 8:29 AM

The podocyte plays a key role in glomerular function and glomerular disease. To facilitate studies of podocyte function, we have developed a transgenic mouse model with inducible expression in the podocyte. The tetracycline-inducible transgenic system facilitates gene expression with restricted cellular distribution and tight temporal control. Recently, Bujard and colleagues have developed a functionally improved reverse tetracycline-controlled transcriptional activator (rtTA) with substantially lower background in the off state (the absence of tetracycline) and greater inducibility in the on state (the presence of tetracycline). We used the human podocin (NPHS2) gene promoter to control expression of the rtTA cassette and bred these mice with a reporter mouse line that contains the cytomegalovirus minimal promoter and tetO promoter elements together with LacZ, encoding beta-galactosidase. Dual transgenic mice, bearing both podocin-rtTA and tetO-LacZ transgenes, had no detectable expression in kidney or other organs in the absence of tetracycline. Administration of tetracycline in the drinking water was associated with podocyte expression of beta-galactosidase, in a fashion that was time dependent (maximal at 1 wk) and dose-dependent (maximal at 2 mg/ml). Podocyte expression was confirmed in two ways: histochemical staining for beta-galactosidase and double-immunostaining using the podocyte marker WT-1 and beta-galactosidase. This transgenic system should aid future investigations of podocyte function.

Research Materials282
  
5′-HS4 chicken β-globin insulatorCell Biology and Physiologyhttp://www.pnas.org/content/101/23/8620.long
Felsenfeld, Gary (NIH/NIDDK) [E]
YesYesYes4/4/2014 8:28 AM

A newly characterized chromatin insulator element isolated from the DNA of a higher eukaryotic organism and contained in vector constructs is described. The insulator element of the invention comprises a DNA sequence which contains a 5’ constitutive hypersensitive site whose functional activity and biochemical characterization as a pure insulator were previously unknown. A core DNA sequence having strong insulator activity is described. The insulator element, including the core sequence, have been demonstrated for the first time in mammalian cells to function to buffer or insulate an expressed gene from the activity of cis-acting regulatory elements, such as enhancers, in the surrounding chromatin or DNA. (US Patent 5,610,053)

Research Materials292
  
Animal Modelshttp://mammary.nih.gov/models/index.html
Hennighausen, Lothar Dr. (NIH/NIDDK) [E]
YesYesNo4/4/2014 8:27 AM

A guide to animal models which have been used to study molecular mechanisms of Mammary Gland Development, Physiology and Tumorigenesis.

Research Materials324
  
http://www.revolutionnmr.com/Tycko_Probe_Data_Sheet_ENC_2012.pdf
Thurber, Kent (NIH/NIDDK) [E]
YesYesNo4/4/2014 8:26 AM

A Nuclear Magnetic Resonance (NMR) probe is a device that inserts into the magnet of an NMR spectrometer and contains both the radio-frequency circuitry for NMR experiments and the sample of interest. Magic-angle Spinning (MAS) is a technique in which the sample is rotated around an axis inclined at a 54.7 degree angle to the external magnetic field during experiments. This is a collaboration to produce a NMR probe capable of performing experiments on biochemical samples with MAS at sample temperatures of approximately 25 K.

Research Materials322
  
http://patft.uspto.gov/netacgi/nph-Parser?Sect1=PTO2&Sect2=HITOFF&u=%2Fnetahtml%2FPTO%2Fsearch-adv.htm&r=3&f=G&l=50&d=PTXT&p=1&S1=7759643&OS=7759643&RS=7759643
Lloyd, John (NIH/NIDDK) [E]
YesYesNo4/4/2014 1:01 AM

A single electrode electrochemical/electrospray ionization source using a corona discharge and a method of analyzing a sample using a corona discharge single electrode electrochemical/electrospray ionization source are provided. In the corona discharge single electrode electrochemical/electrospray ionization technique electrons are removed from the metal tip of the device through gases present in the electrospray ion source resulting in electrochemical ionization of the sample of interest. The resulting odd electron sample cation (positive ion mode) or anion (negative ion mode) can then be analyzed by an appropriate technique, such as, for example, a mass spectrometer.

Research Materials338
  
http://patft.uspto.gov/netacgi/nph-Parser?Sect1=PTO2&Sect2=HITOFF&u=%2Fnetahtml%2FPTO%2Fsearch-adv.htm&r=5&f=G&l=50&d=PTXT&p=1&S1=6387662&OS=6387662&RS=6387662
Liang, Jake (NIH/NIDDK) [E]
YesYesNo4/4/2014 12:59 AM

Production of enveloped RNA virus-like particles intracellularly in vitro in insect cells using a recombinant baculovirus vector containing a cDNA coding for viral structural proteins is disclosed. In vitro production and purification of hepatitis C virus (HCV)-like particles containing HCV core protein, E1 protein and E2 protein is disclosed. Production of antibodies in vivo to the purified HCV-like particles is disclosed.

Research Materials320
  
http://patft.uspto.gov/netacgi/nph-Parser?Sect1=PTO2&Sect2=HITOFF&u=%2Fnetahtml%2FPTO%2Fsearch-adv.htm&r=23&f=G&l=50&d=PTXT&p=1&S1=5872210&OS=5872210&RS=5872210
Louis, John (NIH/NIDDK) [E]
YesYesNo4/4/2014 12:58 AM

The present invention describes small, water soluble peptides isolated from a native virus inhibitory sequence that blocks maturation of the virally encoded protease and inhibits the mature protease as well. The peptides may be used in the treatment of virally infected cells, in the preparation of vaccine formulations, in the generation of clinically relevant antibodies and anti-idiotypic antibodies and in the generation of a screening assay or kit that can be used to identify other similarly acting protease inhibitors.

Research Materials346
  
http://www.google.com/patents/WO2003094860A3
Agarwal, Sunita (NIH/NIDDK) [E]
YesYesNo4/4/2014 12:57 AM

The present invention provides an isolated or purified oligonucleotide consisting essentially of the nucleotide sequence of Clorf28 and comprising a mutation; a fragment of the oligonucleotide; a vector comprising the oligonucleotide or fragment thereof; a cell comprising the vector; an isolated or purified polypeptide encoded by the above oligonucleotide or fragment thereof; a method of detecting HPT-JT or a predisposition to HPT-JT in a human, which method comprises detecting either at least one mutation in a nucleic acid comprising the nucleotide sequence of C1orf28 or a mutant C1orf28 protein; and an antibody which binds to a mutant C1orf28 protein.

Research Materials334
  
http://appft1.uspto.gov/netacgi/nph-Parser?Sect1=PTO1&Sect2=HITOFF&d=PG01&p=1&u=/netahtml/PTO/srchnum.html&r=1&f=G&l=50&s1=20070099836.PGNR.
Gorden, Phillip (NIH/NIDDK) [E]
YesYesNo4/4/2014 12:56 AM

Leptin, leptin analogs, and leptin derivatives are used to treat patients with lipoatrophy. Leptin is effective against conditions of lipoatrophy for both genetic and acquired forms of the disease. A therapeutically effective amount of leptin can be administered in a variety of ways, including subcutaneously and using gene therapy methods. Methods of the present invention contemplate administration of leptin, leptin analogs, and leptin derivatives to patients having a leptin level of approximately 4 ng/ml or less before treatment.

Research Materials340
  
http://www.google.com/patents/US20070154569
Schechter, Alan N (NIH/NIDDK) [E]
YesYesNo4/4/2014 12:55 AM

It has been surprisingly discovered that administration of nitrite to subjects causes a reduction in blood pressure and an increase in blood flow to tissues. The effect is particularly beneficial, for example, to tissues in regions of low oxygen tension. This discovery provides useful treatments to regulate a subject's blood pressure and blood flow, for example, by the administration of nitrite salts. Provided herein are methods of administering a pharmaceutically-acceptable nitrite salt to a subject, for treating, preventing or ameliorating a condition selected from: (a) ischemia-reperfusion injury (e.g., hepatic or cardiac or brain ischemia-reperfusion injury); (b) pulmonary hypertension (e.g., neonatal pulmonary hypertension); or (c) cerebral artery vasospasm.

Research Materials291
  
Mutant Mouse:  GNAS (guanine nucleotide binding protein, alpha stimulating)Endocrine Disease and Metabolic DiseaseAnimal ModelsDevelopmental Biologyhttp://www.ncbi.nlm.nih.gov/pubmed/16239968
Weinstein, Lee Dr. (NIH/NIDDK) [E]
YesYesYes4/4/2014 12:54 AM

Generation of a floxed Gnsa gene for the G-protein Gsα for the construction of conditional knockout mice.

 

The heterotrimeric G protein Gsa couples many receptors to adenylyl cyclase and is essential for hormone-stimulated cAMP generation.  Previous mouse models with germ-line mutations in Gnas, the gene that encodes Gsa had limited usefulness in trying to decipher the role of Gsa pathways in specific tissues since only heterozygotes were viable and could be analyzed. Analysis was further complicated by the fact that Gsa is imprinted expressed in many metabolically active tissues.

 

Gsa-floxed mice were generated so that the metabolic effects of Gsa deficiency could be examined in specific tissues. Exon1, which is specific for Gsa, was surrounded with loxP recombination sites.  Liver-specific knockouts of Gsa were obtained by mating the Gsa - floxed mice with albumin promoter-Cre-transgenic mice.  Gsa exon1 was efficiently deleted. These mice have been used successfully to generate other tissue-specfic Gsa knockout mice.

Research Materials358
  
http://www.google.com/patents/US8153781
Jacobson, Kenneth (NIH/NIDDK) [E]
NoYesNo4/4/2014 12:53 AM

Disclosed are conjugates comprising a dendrimer and a ligand, which is a functionalized congener of an agonist or antagonist of a receptor of the G-protein coupled receptor (GPCR) superfamily, for example, wherein the functionalized congener is an A1 adenosine receptor agonist having a purine nucleoside moiety and a functional group at the N6 position of the purine nucleoside moiety, wherein the functional group has the formula (I):
N6H—Ar1—CH2—C(═O)NH—R1 (I), wherein Ar1 and R1 as defined herein. Also disclosed are pharmaceutical compositions, methods of treating various diseases, and a diagnostic method employing such conjugates.​

Research Materials359
  
http://www.google.com/patents/US7790735
Jacobson, Kenneth (NIH/NIDDK) [E]
NoYesNo4/4/2014 12:48 AM

The present invention provides novel nucleoside and nucleotide derivatives that are useful agonist or antagonists of P1 and P2 receptors. For example, the present invention provides a compound of formula A-M, wherein A is modified adenine or uracil and M is a constrained cycloalkyl group. The adenine or uracil is bonded to the constrained cycloalkyl group. The compounds of the present invention are useful in the treatment or prevention of various diseases including airway diseases (through A2B, A3, P2Y2 receptors), cancer (through A3, P2 receptors), cardiac arrhythmias (through A1 receptors), cardiac ischemia (through A1, A3 receptors), epilepsy (through A1, P2X receptors), and Huntington's Disease (through A2A receptors).​

Research Materials362
  
http://patft.uspto.gov/netacgi/nph-Parser?Sect1=PTO2&Sect2=HITOFF&u=%2Fnetahtml%2FPTO%2Fsearch-adv.htm&r=15&f=G&l=50&d=PTXT&p=1&p=1&S1=Jacobson-kenneth-a$.INNM.&OS=IN/Jacobson-kenneth-a$&RS=IN/Jacobson-kenneth-a$
Jacobson, Kenneth (NIH/NIDDK) [E]
NoYesNo4/4/2014 12:47 AM

The present invention provides a method of identifying CFTR-binding compounds for treating cells having a reduced apical Cl.sup.- conductance, such as cystic fibrosis cells. This identification method involves the use of polypeptide I.alpha., which constitutes a portion of the CFTR protein. The present invention also provides a method of treating CF cells by contacting cells having a reduced apical Cl.sup.- conductance with a therapeutically effective quantity of a compound selected by the present inventive identification method. Preferred compounds for such treatment have little or no affinity for adenosine cell receptors. The present invention provides novel compounds useful in practicing the present inventive method, as well as pharmaceutical compositions containing such compounds. ​

Research Materials363
  
http://www.google.com/patents/US5366977
Jacobson, Kenneth (NIH/NIDDK) [E]
NoYesNo4/4/2014 12:46 AM

A method of treating cells having a reduced apical Cl.sup.- conductance, such as that characteristic of cystic fibrosis cells, by contacting cells having a reduced apical Cl.sup.- conductance with a therapeutically effective quantity of a compound that antagonizes the A.sub.1 -adenosine cell receptor and does not antagonize the A.sub.2 -adenosine cell receptor. Suitable compounds include 8-cyclopentyl-1,3-dipropylxanthine (CPX), xanthine amino congener (XAC), and therapeutically effective derivatives thereof.​

Research Materials364
  
http://www.google.com/patents/US20110046166
Jacobson, Kenneth (NIH/NIDDK) [E]
NoYesNo4/4/2014 12:45 AM

Disclosed are (N)-methanocarba adenine nucleosides, e.g., of formula (I) as highly potent A3 adenosine receptor agonists, pharmaceutical compositions comprising such nucleosides, and a method of use of these nucleosides, wherein R1-R6 are as defined in the specification. These nucleosides exhibit similar selectivities as agonists of the A3 versus the A1 receptor for both human and mouse adenosine receptors, and are contemplated for use in the treatment a number of diseases, for example, inflammation, cardiac ischemia, stroke, asthma, diabetes, and cardiac arrhythmias. ​

Research Materials365
  
http://www.google.com/patents/US20110171130
Jacobson, Kenneth (NIH/NIDDK) [E]
NoYesNo4/4/2014 12:44 AM

Disclosed are A3 adenosine receptor antagonists and/or partial agonists of formula (I): wherein R1 to R5 are as described herein, as well as pharmaceutical compositions thereof and methods of use thereof. The antagonists or partial agonists find use in treating a number of diseases including cancer, glaucoma, inflammatory diseases, asthma, stroke, myocardial infarction, allergic reactions, rhinitis, poison ivy induced responses, urticaria, scleroderma, arthritis, brain arteriole diameter constriction, bronchoconstriction, and myocardial ischemia, as well as in preventing cardiac ischemia. Also disclosed are radiolabeled compounds of formula (I) and the use thereof in diagnostic imaging of tissues and organs.​

Research Materials367
  
http://www.google.com/patents/US7787930
Ouwerkerk, Ronald (NIH/NIDDK) [E]
NoYesNo4/4/2014 12:43 AM

Adiabatic pulses that define an amplitude modulation and a frequency modulation are applied in a sequence of pulses to obtain a T2 weighted magnetic resonance image. Such an adiabatic T2 prep sequence typically includes a first 90° pulse, an even number of adiabatic pulses, and a second 90° pulse. Adiabatic pulses can be selected based on function pairs, or can be defined numerically. A magnetic resonance imaging (MRI) system includes a library of adiabatic pulse waveforms, and is configured to select a waveform and apply an RF magnetic field based on the selected pulse waveform.​

Research Materials361
  
http://patft.uspto.gov/netacgi/nph-Parser?Sect1=PTO2&Sect2=HITOFF&u=%2Fnetahtml%2FPTO%2Fsearch-adv.htm&r=10&f=G&l=50&d=PTXT&p=1&p=1&S1=Jacobson-kenneth-a$.INNM.&OS=IN/Jacobson-kenneth-a$&RS=IN/Jacobson-kenneth-a$
Jacobson, Kenneth (NIH/NIDDK) [E]
NoYesNo4/4/2014 12:43 AM

This invention relates to a method of decreasing intraocular pressure by administrating an A3 subtype adenosine receptor antagonist, a calmodulin antagonist or an antiestrogen such as tamoxifen. ​

Research Materials357
  
(N)-Methanocarba Adenosine Derivatives and Their Dendrimer Conjugates as A3 Receptor Agonists (U.S. Patent Application Number 61/313,961)
Jacobson, Kenneth (NIH/NIDDK) [E]
NoYesNo4/4/2014 12:42 AM

Disclosed are (N)-methanocarba adenine nucleosides, e.g., of the formula (I): as A3 adenosine receptor agonists, pharmaceutical compositions comprising such nucleosides, and a method of use of these nucleosides, wherein A, a, R2, and R3 are as defined in the specification. These nucleosides are contemplated for use in the treatment a number of diseases, for example, inflammation, cardiac ischemia, stroke, asthma, diabetes, and cardiac arrhythmias. Also disclosed are conjugates comprising a dendrimer and one or more ligands, which are functionalized congeners of an agonist or antagonist of a receptor of the G-protein coupled receptor (GPCR) superfamily. Such conjugates are have the potential of being used as dual agonists, dual antagonists, or agonist/antagonist combinations.​

Research Materials360
  
http://www.google.com/patents/US6528516
Jacobson, Kenneth (NIH/NIDDK) [E]
NoYesNo4/4/2014 12:40 AM

This invention relates to a method of decreasing intraocular pressure by administrating an A3 subtype adenosine receptor antagonist, a calmodulin antagonist or an antiestrogen such as tamoxifen.​

Research Materials368
  
http://www.google.com/patents/US7375520
Ouwerkerk, Ronald (NIH/NIDDK) [E]
NoYesNo4/4/2014 12:39 AM

A T2 preparation sequence uses a segmented BIR-4 adiabatic pulse with two substantially equal delays and is insensitive to B1 field variations and can simultaneously suppress fat signals with low specific absorption rate (SAR). An adiabatic reverse half passage pulse is applied followed by a predetermined delay. An adiabatic full passage pulse is applied followed by a substantially equal delay, followed by an adiabatic half passage pulse. Fat signal suppression is achieved by increasing or decreasing either the first delay or the second delay.​​

Research Materials306
  
Mutant Mouse:  Transgene expresess the tetracycline-inhibitable transcription factor driven by the mouse albumin promoterHematologic DiseaseAnimal Modelshttp://www.ncbi.nlm.nih.gov/pubmed/11278564
Liang, Jake (NIH/NIDDK) [E]
YesYesYes4/4/2014 12:39 AM

Tetracycline-responsive transcriptional activator driven by the liver-specific mouse albumin promoter (Alb-tTA)

 
The E. Coli tetracycline operon regulatory system was used to generate a liver-specific transcription activation system that was inhibited by tetracycline.  The transcription activator was a fused protein consisting of a tetracycline repressor gene (tetR) that was only active in the presence of tetracycline and a herpes simplex virus protein (VP-16) transcription activating domain.  Transcription was induced only in the absence of tetracycline (Tet-Off).  A liver-specific promoter such as mouse albumin determined that the tetracycline-regulated transcriptional activator (tTA) would be expressed specifically in liver.  To study the effect of the transcription activator on a target gene (for example, Simian Virus 40 (SV4) large tumor (T) antigen (TAg)) specifically in liver, Alb-tTA mice were mated with transgenic mice in which the Target gene (TAg) was controlled by the E.Coli Tetracycline Operator (Tet-O).  In this example, TAg was expressed in hepatocytes in the absence of Tetracycline, leading to hepatoma formation.  When the mice were treated with tetracycline, TAg was not expressed and hepatomas did not form.
Research Materials369
  
Yuen, Peter (NIH/NIDDK) [E]
YesYesYes4/4/2014 12:38 AM

NIDDK investigators have developed a synthetic polypeptide with beneficial effects and prospective treatment of chronic kidney disease (CKD).  End stage renal disease (ESRD) is a major health and economic burden and requires transplantation or dialysis to avoid imminent death. ESRD is the final stage of CKD, which progresses over the course of decades. The major causes of CKD are diabetes and hypertension, and treatments for diabetes and hypertension are only partially effective to slow the progression of CKD. Only one class of drugs Angiotensin Converting Enzyme inhibitors and/or Angiotensin Receptor Blockers (ACEi/ARB) is effective for slowing CKD progression, but many CKD patients, especially African Americans, are resistant to ACEi/ARB therapy. Several anti-oxidant/anti-fibrotic agents (including bardoxolone and pirfenidone) have not shown efficacy in recent clinical trials. Therefore, novel therapeutic approaches are needed for this large unmet medical need.  The investigators previously demonstrated in a mouse preclinical model that CD36 is important for developing CKD, where deletion of the CD36 gene prevented most of the progression of CKD. Subsequently, they tested whether peptides designed to inhibit CD36 action could also prevent the progression of CKD.


CKD is highly prevalent in the US, affecting more than 20 million people. African Americans have a higher risk than Caucasians.
Research Materials307
  
Mutant Mouse:  Transgene expresess the tetracycline-inhibitable transcription factor driven by the mouse major urinary protein promoterHematologic DiseaseAnimal Modelshttp://www.ncbi.nlm.nih.gov/pubmed/11278564
Liang, Jake (NIH/NIDDK) [E]
YesYesYes4/3/2014 10:52 PM

Tetracycline-responsive transcriptional activator driven by the liver-specific mouse major urinary protein promoter (MUP-tTA)

 

The E. Coli tetracycline operon regulatory system was used to generate a liver-specific transcription activation system that was inhibited by tetracycline.  The transcription activator was a fused protein consisting of a tetracycline repressor gene (tetR) that was only active in the presence of tetracycline and a herpes simplex virus protein (VP-16) transcription activating domain (Tet-Off).  Transcription was induced only in the absence of tetracycline (Tet-Off).  A liver-specific promoter such as the mouse major urinary protein (MUP) promoter determined that the tetracycline-regulated transcriptional activator (tTA) would be expressed specifically in liver.  To study the effect of the transcription activator on a target gene (for example, beta-galactosidase, LacZ) specifically in liver, MUP-tTA mice would be mated with transgenic mice in which the TAg Target gene was controlled by the E.Coli Tetracycline Operator (Tet-O).

Research Resources263
  
RKSCKidney Disease; Urologic DiseaseBiomarkers; Biosamples; Tissues; DNA; Datasets; Protocols and Methods; PhenotypingGenetics and Genomics; Clinical Research; Ancillary Studies; Behavior; Biomarker Development; Epidemiology; Translation; Imaging and Biotechnology; Systems Biology; Bioinformatics; Biostatistics; Integrative biology; Omicshttp://www.rarekidneystones.org/Rasooly, Rebekah (NIH/NIDDK) [E]NoNoNo12/17/2013 12:01 PM

The Consortium facilitates cooperative exchange of information and resources among investigators, clinicians, patients, and researchers in order to improve care and outcomes for patients with rare stone diseases.  The consortium promotes ready availability of diagnostic testing, pooling of clinical experiences, and availability of tissue banks in order to advance the science.

Research Resources201
  
HAPO-FUSDiabetes; Digestive Disease; ObesityBiosamples; DatasetsClinical Research; Ancillary Studies; Pediatrics; Women's Healthhttp://www.niddkrepository.org/studies/hapo-fus/Horlick, Mary (NIH/NIDDK) [E]NoNoNo12/17/2013 11:12 AM

The goal of this follow-up study of mothers who participated in the Hyperglycemia and Adverse Pregnancy Outcomes (HAPO) study, is to determine the levels of blood sugar during pregnancy that are linked to increased body fat in the child, and to a moether's chances of developing diabetes 8-12 years after the pregnancy.  The original study examined 23,316 mother-child pairs, and researchers determined that a mother's hyperglycemia was linked to newborn birth weight and body fat.  HAPO-FUS will enroll 7,000 or the original HAPO mother-child pairs for one follow-up visit to assess body composition, blucose metabolism, medical history, and other metabolic parameters.

Research Resources264
  
RIVURKidney Disease; Urologic DiseaseBiomarkers; Biosamples; DNA; Tissues; Datasets; Protocols and Methods; PhenotypingGenetics and Genomics; Clinical Research; Ancillary Studies; Behavior; Biomarker Development; Epidemiology; Translation; Imaging and Biotechnology; Systems Biology; Bioinformatics; Biostatistics; Integrative biology; Omics; Pediatricshttps://www.niddkrepository.org/studies/rivur/Moxey-Mims, Marva (NIH/NIDDK) [E]NoNoNo12/11/2013 3:47 PM

The purpose of this study is to learn whether all children with vesicoureteral reflux (VUR) should be treated with antibiotics. The study will tell us if prophylactic antibiotic treatment prevents urinary tract infections and renal scarring in children with VUR. More information at ClinicalTrials.gov.

Research Resources328
  
http://patft.uspto.gov/netacgi/nph-Parser?Sect1=PTO2&Sect2=HITOFF&p=1&u=%2Fnetahtml%2FPTO%2Fsearch-bool.html&r=1&f=G&l=50&co1=AND&d=PTXT&s1=%22Receptors+regulate+cell+signaling+relating+chemokines%22&OS=Gershengorn, Marvin (NIH/NIDDK) [E]NoNoNo11/29/2013 10:17 AM

A method for discovering molecules that regulate cell signaling specific to the dual presence of Duffy antigen receptor for chemokines (DARC) and a chemokine receptor selected from the group consisting of a CXC receptor, a CC receptor and a CXXXC receptor, the method comprising providing a cell that co-expresses DARC and the chemokine receptor; incubating the molecules with the cell; measuring the cell signaling in the cell specific to the dual presence of DARC and the chemokine receptor; and determining whether the cell signaling specific to the dual presence of DARC and the chemokine receptor is regulated by the molecules.

Research Resources327
  
http://patft.uspto.gov/netacgi/nph-Parser?Sect1=PTO2&Sect2=HITOFF&p=1&u=%2Fnetahtml%2FPTO%2Fsearch-bool.html&r=1&f=G&l=50&co1=AND&d=PTXT&s1=%22Pituitary+TRH+receptor%22&OS=Gershengorn, Marvin (NIH/NIDDK) [E]NoNoNo11/29/2013 10:15 AM

Disclosed for the first time is the isolation, sequence, and expression cloning of a cDNA encoding for pituitary thyrotropin-releasing hormone receptor, as well as the amino acid sequence for the receptor per se.

Research Resources195
  
EPISODLiver DiseaseBiosamplesClinical Research; Interventional Trialhttp://www.episodstudy.org/Sherker, Averell (NIH/NIDDK) [E]NoNoNo11/27/2013 10:23 AM

The EPISOD study is a prospective, double-blind, randomized, sham-controlled, multi-center clinical trial. The EPISOD study enrolls subjects who have received a prior cholecystectomy and are diagnosed with the clinical syndrome of Sphincter of Oddi Dysfunction III (SOD III) as defined by the Rome III criteria. The goal of the EPISOD study is to asses the value of endoscopic sphincterotomy as a treatment for adult subjects categorized as SOD III suffering from pain after cholecystectomy and to define the role of manometry in treating these patients.

Research Resources194
  
GLNDNutritionClinical Research; Ancillary Studies; Interventional TrialEvans, Mary (NIH/NIDDK) [E]NoNoNo11/27/2013 10:21 AM

The GLND trial is a multi-center, double-blind, placebo-controlled, intent-to-treat Phase III trial, designed to determine the effect of parenteral glutamine (GLN) dipeptide on important clinical outcomes in patients requiring surgical intensive care unit (SICU) care and parenteral nutrition after cardiac, vascular, or intestinal surgery. Patients who required PN and SICU care will receive either standard glutamine (GLN)-free PN (STD-PN) or isocaloric, isonitrogenous alanyl-glutamine dipeptide (AG)-PN until enteral feedings are established. The study will determine whether AG-PN decreases hospital mortality, nosocomial infection and other important indices of morbidity and will obtain mechanistically relevant observational data in the subjects on whether AG-PN a) increases serial blood concentrations of glutathione (GSH), heat shock proteins (HSP)-70 and -27, and glutamine; b) decreases the serum presence of the bacterial products flagellin and lipopolysaccharide (LPS) and the adaptive immune response to these mediators; and c) improves key indices of innate and adaptive immunity. Follow-up of GLND study participants ended in March 2012.

Research Resources187
  
ALFSGLiver DiseaseBiomarkers; Biosamples; Tissues; DatasetsGenetics and Genomics; Clinical Research; Ancillary Studies; Epidemiology; Interventional Trial; Transplantationhttp://www.utsouthwestern.edu/labs/acute-liver/about/Sherker, Averell (NIH/NIDDK) [E]NoNoNo11/16/2013 3:27 PM
The Acute Liver Failure Study Group is collecting biosamples and information on the natural history, causes and outcomes of Acute Liver Failure in the United States. In addition to the database, a clinical trial conducted to test whether the drug N-acetylcysteine (NAC) improves outcome (survival) for patients with Acute Liver Failure not caused by acetaminophen overdose has recently been completed.
Research Resources237
  
ACCORDIONDiabetes; Endocrine Disease and Metabolic Disease; Kidney Disease; Liver Disease; Nutrition; ObesityBiosamplesAncillary Studies; Behavior; Biomarker Development; Comparative Effectiveness Research; Epidemiology; Health Disparities; Interventional Trial; Pediatrics; Racial Disparities; Translation; Women's Healthhttps://www.accordionstudy.org/public/dspHome.cfmMalozowski, Saul (NIH/NIDDK) [E]NoNoNo11/16/2013 3:26 PM
ACCORDION (sponsored by NHLBI) is a prospective, observational follow-up study of at least 8000 participants who were treated and followed in the Action to Control Cardiovascular Risk in Diabetes (ACCORD) Trial.  Treatment in ACCORD ended in 2009 and ACCORDION is designed to further elucidate the long-term effects of the ACCORD treatment strategies and provide additional data on the relationships among various cardiovascular and diabetic risk factors.
Research Resources16
  
Look AHEADDiabetes; ObesityBiosamples; DNA; TissuesClinical Research; Ancillary Studies; Comparative Effectiveness Research; Interventional Trialhttps://www.niddkrepository.org/studies/look-ahead/https://www.lookaheadtrial.orgEvans, Mary (NIH/NIDDK) [E]NoNoNo11/16/2013 3:26 PM
Look AHEAD is a 16-center, randomized clinical trial investigating the long-term health effects of an intensive lifestyle intervention designed to produce weight loss. Look AHEAD enrolled 5,145 overweight or obese participants with type 2 diabetes, ages 45-76. Participants were randomized to one of two interventions: an intensive lifestyle intervention or a control condition, diabetes support and education arm. The primary hypothesis is that the incidence rate of the first post-randomization occurrence of a composite outcome, which includes fatal and non-fatal myocardial infarction, fatal and non-fatal stroke, hospitalized angina, and cardiovascular death will be reduced among participants assigned to the lifestyle Intervention compared to those assigned to the control condition. Follow-up was planned for a period of up to 13.5 years after randomization.

The Look AHEAD intensive lifestyle intervention ended September, 2012. Participants continue to be followed to determine the long-term effects of the intervention on health outcomes.
Research Resources245
  
DiaCompDiabetes; Digestive Disease; Endocrine Disease and Metabolic Disease; Hematologic Disease; Kidney Disease; Liver Disease; Nutrition; Obesity; Pancreatic Disease; Urologic DiseaseModel Systems; DNA; Tissues; Datasets; Animal Models; Protocols and Methods; Histology; Morphology; Phenotyping; ReagentsGenetics and Genomics; Cell Biology and Physiology; Developmental Biology; Stem Cell Biology; Pathobiology; Fibrosis; Imaging and Biotechnology; Immunology and Inflammation; Systems Biology; Bioinformatics; Biostatistics; Integrative biology; Omics; Pharmacogenomicswww.diacomp.orgKetchum, Chris (NIH/NIDDK) [E]NoNoNo11/14/2013 3:49 PM
The goal of the NIDDK-sponsored Diabetic Complications Consortium (DiaComp) is to foster communication and collaboration between investigator communities involved in complications research.  Toward this goal, DiaComp: (1) sponsors annual meetings in complications-relevant scientific areas; (2) solicits and funds pilot projects in high impact areas of complications research; and (3) supports a website to serve the diabetic complications community.
Research Resources197
  
GpCRCDigestive DiseaseBiosamples; DNA; Datasets; Protocols and Methods; HistologyCell Biology and Physiology; Pathobiology; Clinical Research; Interventional Trial; Women's Healthhttp://www.jhucct.com/gpcrcHamilton, Frank (NIH/NIDDK) [E]NoNoNo11/14/2013 12:59 PM

The GpCRC is focusing on the etiology, natural history, and therapy of gastroparesis. The goal of this consortium is to perform clinical, epidemiological, and therapeutic research in gastroparesis and provide an infrastructure that can rapidly and efficiently design and conduct clinical trials for effective medical, surgical, or other interventions to improve treatment of patients with gastroparesis. The GpCRC studies comprise well characterized individuals with diabetic, surgical, and idiopathic gastroparesis.

Research Resources251
  
UDAUrologic DiseaseDatasets; PhenotypingClinical Research; Behavior; Comparative Effectiveness Research; Epidemiology; Health Disparities; Pediatrics; Racial Disparitieshttp://www.niddk.nih.gov/about-niddk/strategic-plans-reports/Pages/urologic-diseases-america.aspxEggers, Paul (NIH/NIDDK) [E]NoNoNo11/13/2013 3:01 PM

Urologic diseases cover a wide range of conditions, symptoms, and problems that include such diverse diagnoses as cancer, pelvic pain, sexual dysfunction, urinary incontinence, kidney stones, and benign prostatic hyperplasia (BPH). To remedy this lack of information, NIDDK initiated the Urologic Disease in America (UDA) project. The UDA compendium delineates the changes in the epidemiology, health economic impact, and practice patterns for the diseases currently included within the scope of practice of the specialty of urology, analyzed retrospectively over a ten-year period. The UDA compendium consists of data tables annotated in chapters that amplify the data analyses. The objectives of the UDA project include secondary data analyses of the following topics: (1) changes in the overall health care burden for individual urologic diseases; (2) changes in physician practice patterns for each urologic disease; (3) changes in demographics of persons with urologic disease; (4) the impact of specific urologic diseases, especially diseases of the prostate, on the minority populations of the U.S.; (5) documentation of new and evolving therapies for urologic disease and their potential impact on treatment outcomes and health care costs. The resultant compendium can be found at the above web address. In addition to updating the original compendium, the second phase of the UDA is to focus less on descriptive analyses and more on analytical outcomes analyses, and it will also attempt to increase involvement of the urologic community in analytical activities.

Research Resources250
  
USRDSKidney DiseaseDatasets; PhenotypingClinical Research; Ancillary Studies; Behavior; Comparative Effectiveness Research; Epidemiology; Health Disparities; Transplantation; Women's Health; Systems Biology; Biostatisticshttp://www.usrds.org/http://www.niddk.nih.gov/about-niddk/strategic-plans-reports/Pages/US-renal-data-system-report.aspxEggers, Paul (NIH/NIDDK) [E]NoNoNo11/13/2013 2:50 PM

The United States Renal Data System (USRDS) is a national data system that collects, analyzes, and distributes information about end-stage renal disease (ESRD) in the United States. The USRDS is funded directly by the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK). USRDS staff collaborates with members of Centers for Medicare & Medicaid Services (CMS), the United Network for Organ Sharing (UNOS), and the ESRD networks, sharing datasets and actively working to improve the accuracy of ESRD patient information.

Research Resources205
  
LIFE-MomsObesityBiosamplesClinical Research; Ancillary Studies; Behavior; Interventional Trial; Pediatrics; Women's Healthhttps://portal.bsc.gwu.edu/web/lifemomsEvans, Mary (NIH/NIDDK) [E]NoNoNo11/13/2013 2:40 PM

LIFE-Moms is a consortium comprised of seven clinical centers, a Research Coordinating Unit and NIH program staff.  The overall goal of the Consortium is to identify effective behavioral and lifestyle interventions that will improve weight, glycemic control and other-pregnancy-related outcomes in obese and overweight pregnant women, and determine whether these interventions reduce obesity and metabolic abnormalities in their children.  Each clinical center will conduct its own trial.

 

The objective of the collaboration is to maximize the value of the individual trials by identifying core measures collected across all seven studies and ensuring consistency of procedures, certain eligibility criteria, definitions and data collection.  Additional information on the Consortium and individual trials is located in the Consortium Summaries tab at www.portal.bsc.gwu.edu/web/lifemoms.

 

LIFE-Moms is funded by NIDDK, NHLBI, NICHD, NCCAM, ORWH and OBSSR.

Research Resources203
  
ISCCDigestive DiseaseModel Systems; Animal Models; Protocols and Methods; Reagents; AntibodiesCell Biology and Physiology; Stem Cell Biologyhttp://iscc.coh.org/Carrington, Jill (NIH/NIDDK) [E]NoNoNo11/13/2013 2:16 PM

The mission of the ISCC is to advance the understanding of intestinal epithelial stem cell biology during development, homeostasis, regeneration and disease. The immediate goals of the ISCC are to isolate, characterize, culture and validate populations of intestinal stem cells; answer major questions in stem cell biology of the intestinal epithelium; and accelerate research by making information and resources available to the research community.

 

Long-term goals include:  

  1. laying the ground work for therapeutic manipulation of the intestinal epithelium
  2. contributing to the greater understanding of stem cell biology through knowledge of the intestine as a model stem cell-driven system.
Research Resources248
  
MAPPUrologic DiseaseBiomarkers; Biosamples; Tissues; DNA; Datasets; Model Systems; Protocols and Methods; Phenotyping; Animal ModelsGenetics and Genomics; Clinical Research; Ancillary Studies; Behavior; Biomarker Development; Epidemiology; Translation; Women's Health; Imaging and Biotechnology; Systems Biology; Bioinformatics; Biostatistics; Integrative biology; Omicshttp://www.mappnetwork.org/Mullins, Christopher (NIH/NIDDK) [E]NoNoNo11/13/2013 2:13 PM

To help better understand the underlying causes of the two most prominent chronic urological pain syndromes—interstitial cystitis/painful bladder syndrome (IC/PBS) and chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS)—the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) of the National Institutes of Health (NIH), has launched a new and novel research study.

 

The NIDDK’s Multidisciplinary Approach to the Study of Chronic Pelvic Pain (MAPP) Research Network embraces a systemic—or whole-body—approach in the study of IC/PBS and CP/CPPS. In addition to moving beyond traditional bladder- and prostate-specific research directions, MAPP Network scientists are investigating potential relationships between these two urological syndromes and other chronic conditions that are sometimes seen in IC/PBS and CP/CPPS patients, such as irritable bowel syndrome, fibromyalgia, and chronic fatigue syndrome.

 

The multidisciplinary (i.e., scientists employing a variety of research approaches) MAPP Network includes researchers with clinical, epidemiological, and basic research expertise, all working collaboratively.

Research Resources213
  
PROTECTDigestive DiseaseTissues; Biosamples; DNAClinical Research; Ancillary Studies; Pediatricshttp://www.cscc.unc.edu/protect/Serrano, Jose (NIH/NIDDK) [E]NoNoNo11/13/2013 2:09 PM

The mission of the PROTECT Study is to provide a better understanding of how children newly diagnosed with ulcerative colitis (UC) respond to mesalamine and prednisone (corticosteroid), the standard initial therapies used to treat this disorder. PROTECT brings together the experience and resources of 25 highly specialized sites in North America that treat children with UC and the National Institutes of Health (NIH) through the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) which is supporting this study. The PROTECT study is performed in collaboration with the Crohn’s and Colitis Foundation of America (CCFA) using its Pediatric Research Organization for Kids with Intestinal Inflammatory Diseases (PRO-KIIDS) Network.

 

Over a period of 5 years PROTECT will prospectively study the course of 430 children newly diagnosed with UC who are treated with standardized care. Biospecimens (blood, stool, colonic biopsy tissue) will be obtained and used to better understand the effects of genetics, mechanisms of inflammation, Vitamin D, and the bacteria contained in the stool (microbiome) on clinical outcomes.

 

This website is maintained for PROTECT participants, PROTECT investigators, health professionals, and the general public.

Research Resources265
  
LURNUrologic DiseaseBiomarkers; Biosamples; DNA; Tissues; Datasets; Protocols and Methods; PhenotypingGenetics and Genomics; Clinical Research; Ancillary Studies; Behavior; Biomarker Development; Epidemiology; Translation; Imaging and Biotechnology; Systems Biology; Bioinformatics; Biostatistics; Integrative biology; Omicshttps://nih-lurn.org/Kirkali, Ziya (NIH/NIDDK) [E]NoNoNo9/25/2013 3:42 PM

The Symptoms of Lower Urinary Tract Dysfunction Research Network (LURN) is a research consortium funded through the National Institutes of Health (NIH)/National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK).   The long term goal of the LURN network is to develop and test measurement tools to describe symptoms of lower urinary tract dysfunction (LUTD) in women and men. The group plans to study targeted populations of patients with LUTD in order to expand our understanding of the causes of symptoms of LUTD and common ways that symptoms change over time. The researchers will also collect biosamples from patients for current and future study of LUTD. Through these activities, investigators hope that their efforts will inform strategies to prevent and/or manage disease and improve the lives of patients who suffer from the symptoms of LUTD.

Research Resources262
  
Kidney DiseaseBiomarkers; Biosamples; DNA; Tissues; Datasets; Model Systems; Animal Models; Protocols and Methods; PhenotypingGenetics and Genomics; Clinical Research; Ancillary Studies; Behavior; Biomarker Development; Epidemiology; Translation; Imaging and Biotechnology; Systems Biology; Bioinformatics; Biostatistics; Integrative biology; Omicshttp://rarediseasesnetwork.epi.usf.edu/porphyrias/Rasooly, Rebekah (NIH/NIDDK) [E]NoNoNo9/25/2013 3:40 PM

The Porphyrias Consortium includes five of the leading porphyria centers in the United States that provide expertise and experience in the diagnosis and treatment of patients with porphyria. The staff in each Center includes porphyria physicians, researchers, research coordinators, and technical/laboratory staff. Together with the American Porphyria Foundation, the Porphyrias Consortium enables a large scale collaborative effort to develop new strategies and methods for diagnosis, treatment, and prevention of illness and disability resulting from these rare disorders.

Research Resources261
  
NEPTUNEKidney DiseaseBiomarkers; Biosamples; Tissues; DNA; Datasets; Protocols and Methods; PhenotypingGenetics and Genomics; Clinical Research; Ancillary Studies; Behavior; Biomarker Development; Epidemiology; Translation; Imaging and Biotechnology; Systems Biology; Bioinformatics; Biostatistics; Integrative biology; Omicshttps://www.niddkrepository.org/studies/neptune/Moxey-Mims, Marva (NIH/NIDDK) [E]NoNoNo9/25/2013 3:39 PM

The Nephrotic Syndrome Study Network (NEPTUNE) includes patients presenting with significant proteinuria with a clinical indication for a kidney biopsy. The study participants will be classified according to the kidney biopsy results into one of three subcohorts, including Minimal change disease/Focal segmental glomerulosclerosis; Membranous nephropathy; and other conditions.

Research Resources260
  
HALT-PKDKidney DiseaseBiomarkers; Biosamples; Tissues; DNA; Datasets; Protocols and Methods; PhenotypingGenetics and Genomics; Clinical Research; Ancillary Studies; Behavior; Biomarker Development; Epidemiology; Translation; Imaging and Biotechnology; Systems Biology; Bioinformatics; Biostatistics; Integrative biology; Omicshttps://www.niddkrepository.org/studies/halt-pkd/Flessner, Michael (NIH/NIDDK) [E]NoNoNo9/25/2013 3:39 PM

The Polycystic Kidney Disease Treatment Network (PKD-TN) has developed the HALT PKD clinical trials to evaluate certain FDA approved drugs that may be effective in slowing kidney growth in persons who have polycystic kidney disease. Seven centers across the United States are participating in the two trials.

Research Resources259
  
Kidney DiseaseBiomarkers; Biosamples; Tissues; DNA; Datasets; Protocols and Methods; PhenotypingGenetics and Genomics; Clinical Research; Ancillary Studies; Behavior; Biomarker Development; Epidemiology; Translation; Imaging and Biotechnology; Systems Biology; Bioinformatics; Biostatistics; Integrative biology; Omicshttp://www.ckdbiomarkersconsortium.org/Kimmel, Paul (NIH/NIDDK) [E]NoNoNo9/25/2013 3:37 PM

Scientific inquiry into the causes and consequences of chronic kidney disease (CKD) has been hampered by a dearth of blood and urinary markers that predict or reflect disease progression. The National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) established the CKD Biomarkers Consortium to promote the discovery and validation of biomarkers to advance the field of CKD research. The NIDDK CKD Biomarkers Consortium brings together investigators whose expertise includes clinical nephrology, epidemiology, molecular biology, genomics, proteomics, metabolomics, systems biology, laboratory medicine, biostatistics, and laboratory test verification and qualification.

Research Resources258
  
CkiDKidney DiseaseBiomarkers; Biosamples; DNA; Tissues; Datasets; Protocols and Methods; PhenotypingGenetics and Genomics; Clinical Research; Ancillary Studies; Behavior; Biomarker Development; Epidemiology; Translation; Imaging and Biotechnology; Systems Biology; Bioinformatics; Biostatistics; Integrative biology; Omics; Pediatricshttps://www.niddkrepository.org/studies/ckid/http://www.statepi.jhsph.edu/ckid/Moxey-Mims, Marva (NIH/NIDDK) [E]NoNoNo9/25/2013 2:23 PM

The Chronic Kidney Disease in Children Study (CKiD) aims to determine: (1) risk factors for progression of pediatric chronic kidney disease (CKD), (2) the impact of CKD on neurocognitive development, (3) the impact of CKD on risk factors for cardiovascular disease, and (4) the impact of CKD on growth.

Research Resources257
  
CRICKidney DiseaseBiomarkers; Biosamples; DNA; Tissues; Datasets; Protocols and Methods; PhenotypingGenetics and Genomics; Clinical Research; Ancillary Studies; Behavior; Biomarker Development; Epidemiology; Translation; Imaging and Biotechnology; Systems Biology; Bioinformatics; Biostatistics; Integrative biology; Omicshttps://www.niddkrepository.org/studies/cric/http://www.cristudy.org/Chronic-Kidney-Disease/Chronic-Renal-Insufficiency-Cohort-Study/Kusek, John (NIH/NIDDK) [E]NoNoNo9/25/2013 2:22 PM

The CRIC Study is a major national research effort poised to make fundamental insights into the epidemiology, management, and outcomes of chronic kidney disease (CKD). The CRIC Study represents the largest, nationally representative prospective cohort of adults with chronic kidney disease with intended long-term follow up.

Research Resources246
  
Diabetes; Digestive Disease; Endocrine Disease and Metabolic Disease; Hematologic Disease; Kidney Disease; Liver Disease; Nutrition; Obesity; Pancreatic Disease; Urologic DiseaseBiosamples; DNA; Tissues; DatasetsCell Biology and Physiology; Developmental Biology; Fibrosis; Pathobiology; Stem Cell Biology; Clinical Research; Ancillary Studies; Behavior; Biomarker Development; Comparative Effectiveness Research; Epidemiology; Health Disparities; Interventional Trial; Pediatrics; Racial Disparities; Translation; Transplantation; Women's Health; Genetics and Genomics; Imaging and Biotechnology; Immunology and Inflammation; Systems Biology; Bioinformatics; Biostatistics; Integrative biology; Omics; Pharmacogenomicshttps://www.niddkrepository.org/home/Rasooly, Rebekah (NIH/NIDDK) [E]NoNoNo9/25/2013 2:21 PM

Supports Data, Biosample, and Genetic Repositories to increase the impact of current and previously funded NIDDK studies by making their data and biospecimens available to the broader scientific community. These Repositories enable scientists not involved in the original study to test new hypotheses without any new data or biospecimen collection, and they provide the opportunity to pool data across several studies to increase the power of statistical analyses.  In addition, some NIDDK-funded studies are collecting genetic biospecimens and carrying out high-throughput genotyping making it possible for other scientists to use Repository resources to match genotypes to phenotypes and to perform informative genetic analyses.

Research Resources232
  
TEDDYDiabetes; Digestive DiseaseBiosamples; DatasetsClinical Research; Epidemiologyhttp://teddy.epi.usf.edu/https://www.niddkrepository.org/studies/teddy/http://teddy.epi.usf.edu/research/Akolkar, Beena (NIH/NIDDK) [E]NoNoNo9/25/2013 2:20 PM

The TEDDY study - The Environmental Determinants of Diabetes in the Young - is looking for the causes of type 1 diabetes mellitus (T1DM).  Research tells us that children who get diabetes have certain kind of genes. Other children who have these genes are at higher risk for getting diabetes. However, not all children who are higher risk get diabetes.  We think that something happens that "triggers" or causes a child with higher risk genes to actually get diabetes. It is the purpose of this study to try and find out what are the triggers that cause children to get diabetes.

Research Resources227
  
HEALTHYDiabetes; ObesityEpidemiology; Health Disparities; Interventional Trial; Pediatrics; Racial Disparitieshttps://www.niddkrepository.org/studies/healthy/http://www.healthystudy.org/Linder, Barbara (NIH/NIDDK) [E]NoNoNo9/25/2013 2:18 PM

The HEALTHY study, completed in 2009, demonstrated that a middle-school based program to change eating habits and physically activity could reduce the risk of obesity in high risk children. All materials developed for the intervention are publically available.

Research Resources221
  
EDICDigestive Disease; Diabetes; Endocrine Disease and Metabolic Disease; Kidney Disease; Nutrition; Obesity; Urologic DiseaseBiomarkers; DNA; Tissues; Datasets; PhenotypingGenetics and Genomics; Ancillary Studies; Behavior; Biomarker Development; Epidemiology; Health Disparities; Interventional Trial; Pediatrics; Women's Health; Imaging and Biotechnology; Immunology and Inflammationhttps://www.niddkrepository.org/studies/edic/http://archives.niddk.nih.gov/patient/EDIC/EDIC-public.aspxhttp://www2.bsc.gwu.edu/bsc/oneproj.php?pkey=10Cowie, Catherine (NIH/NIDDK) [E]NoNoNo9/25/2013 2:14 PM

An observational study examining the risk factors associated with the long-term complications of type 1 diabetes. The study began in 1994 and follows the 1441 participants previously enrolled in the Diabetes Control and Complications Trial (DCCT).

Research Resources212
  
VIRAHEP-CLiver DiseaseBiosamplesClinical Research; Ancillary Studies; Interventional Trial; Racial Disparitieshttps://www.niddkrepository.org/studies/virahep-c/Doo, Edward (NIH/NIDDK) [E]NoNoNo9/25/2013 2:11 PM

A study conducted at eight clinical sites and included ancillary studies at four additional sites to evaluate factors associated with resistance to antiviral therapy in 400 African American and Caucasian American patients with chronic hepatitis C. All patients were treated with combination therapy of pegylated interferon and ribavirin for 48 weeks, and were followed for an additional 48 week safter cessation of therapy.

Research Resources210
  
Peds-CLiver DiseaseBiosamplesClinical Research; Ancillary Studies; Interventional Trial; Pediatricshttps://www.niddkrepository.org/studies/peds-c/Doo, Edward (NIH/NIDDK) [E]NoNoNo9/25/2013 2:09 PM

This prospective, randomized controlled trial was completed in 2008 and studied peginterferon therapy, with or without ribavirin, in children with chronic hepatitis C. Approximately 120 children were randomly assigned to receive peginterferon alfa-2a alone or peginterferon with ribavirin for 48 weeks. Samples of blood, genomic DNA, and liver tissue are stored in the NIDDK repositories. A long-term follow up study of the clinical trial participants is underway.

Research Resources202
  
IBDGCDigestive DiseaseBiosamples; DNA; Datasets; PhenotypingGenetics and Genomics; Clinical Research; Ancillary Studies; Systems Biology; Bioinformatics; Omics; Racial Disparities; Immunology and Inflammationhttps://www.niddkrepository.org/studies/ibd/http://medicine.yale.edu/intmed/ibdgc/index.aspxKarp, Robert (NIH/NIDDK) [E]NoNoNo9/25/2013 2:08 PM

The NIDDK Inflammatory Bowel Disease Genetics Consortium (IBDGC) consists of investigators from seven sites in the U.S. and Canada, who have recruited a large sample of inflammatory bowel disease patients, their relatives, and control subjects. All of the individuals in this sample have been evaluated according to a standardized protocol for clinical traits related to IBD, and have donated blood samples as a source of DNA. The IBDGC investigators are conducting genetic association studies to identify genes influencing predisposition to IBD. Phenotype and genotype data are available in dbGAP, and DNA samples are available through the NIDDK Genetics Repository.

Research Resources199
  
HALT-C TrialLiver DiseaseBiosamples; DNA; Tissues; Protocols and Methods; HistologyClinical Research; Ancillary Studies; Interventional Trialhttps://www.niddkrepository.org/studies/halt-c/http://www.haltctrial.org/Doo, Edward (NIH/NIDDK) [E]NoNoNo9/25/2013 2:03 PM

This prospective, randomized, controlled clinical trial studied long-term therapy with peginterferon in patients with chronic hepatitis C. Patient enrollment began in 2000 and was completed in 2003 at 10 clinical centers, which were supported by a data coordinating center, virological testing center, and central sample repository. Patients with chronic hepatitis C and advanced fibrosis or cirrhosis on liver biopsy who failed to respond to a previous course of interferon alfa were enrolled in this study. Patients were initially treated with a 24-week course of peginterferon alfa-2a and ribavirin. Patients who remained hepatitis C virus RNA positive were then randomized to receive maintenance, low-dose peginterferon or to be followed on no treatment. Liver biopsies were done before enrollment and after 2 and 4 years of treatment or follow-up. The endpoints were development of cirrhosis, hepatic decompensation, hepatocellular carcinoma, death, or liver transplantation. 1050 patients were randomized and followed through the 4 year randomized phase of the trial and as long as 4 years off treatment.  Serum samples collected at multiple time points, DNA and liver tissue are available for scientific investigation.

Research Resources189
  
A2ALLLiver DiseaseBiomarkers; Biosamples; DNA; Tissues; DatasetsClinical Research; Ancillary Studies; Comparative Effectiveness Research; Transplantationhttps://www.niddkrepository.org/studies/a2all/http://www.nih-a2all.org/Sherker, Averell (NIH/NIDDK) [E]NoNoNo9/25/2013 2:01 PM

This study supports nine liver transplant centers with expertise in adult living-donor liver transplantation (LDLT) and a central data coordinating center. The major aims of A2ALL are as follows:

  • quantify the impact of choosing LDLT on the candidate for transplantation
  • characterize the difference between LDLT and deceased donor liver transplant (DDLT) in terms of post-transplant outcomes, including patient and graft survival, surgical morbidity, and resource utilization on the recipient of a transplant  
  • determine the short- and long-term health and quality of life (QOL) impact of donation, including (a) morbidity after liver donation and (b) long-term health-related QOL of donors
  • standardize and assess the role of "informed consent" in affecting the decision to donate and satisfaction after living liver donation
  • other aims include comparison of the severity of recurrence of hepatocellular carcinoma for DDLT versus LDLT, the systematic characterization of liver regeneration and function in donors and recipients, the evaluation of the differences in the immune response to LDLT versus DDLT, and the establishment of a robust data and sample repository on liver transplantation that may be used to study clinical and biological questions as new technologies and resources become available

Patients enrolled in the study will be followed and managed in a standardized fashion.

Research Resources243
  
D2dDiabetesPhenotyping; Protocols and MethodsClinical Research; Ancillary Studieshttp://www.d2dstudy.org/Staten, Myrlene (NIH/NIDDK) [C]NoNoNo9/23/2013 4:29 PM

The goal of the Vitamin D and type 2 diabetes (D2d) study is to determine whether vitamin D supplementation is safe and effective in delaying the onset of type 2 diabetes in people at risk for the disease and to gain a better understanding of how vitamin D affects glucose metabolism.

Research Resources236
  
T1D-RaidDiabetesProtocols and MethodsSystems Biologyhttp://t1diabetes.nih.gov/T1D-RAID/Pawlyk, Aaron (NIH/NIDDK) [E]NoNoNo9/23/2013 4:23 PM

The Type 1 Diabetes - Rapid Access to Intervention Development (T1D-RAID) program is designed to assist translation to the clinic of novel therapeutic interventions for type 1 diabetes and its complications. These potential interventions can be either synthetic, natural product, or biologic. Requests to T1D-RAID are brief (20 pages or less), and should clearly outline the resources required to ready the proposed therapeutic agent for clinical trials.

Research Resources235
  
TrialNetDiabetes; Pancreatic DiseaseBiomarkers; Biosamples; DNA; Tissues; Datasets; AntibodiesGenetics and Genomics; Ancillary Studies; Behavior; Biomarker Development; Comparative Effectiveness Research; Epidemiology; Interventional Trial; Pediatrics; Translation; Imaging and Biotechnology; Immunology and Inflammation; Biostatisticshttp://www.diabetestrialnet.org/http://www.diabetestrialnet.org/ancillary/Leschek, Ellen (NIH/NIDDK) [E]NoNoNo9/23/2013 4:22 PM

Type 1 Diabetes TrialNet (TrialNet) is an international network of researchers who are exploring ways to prevent, delay and reverse the progression of type 1 diabetes.

Research Resources234
  
T1DRDiabetesAnimal Models; Protocols and Methods; Biosamples; Cell Lines; Reagentshttp://type1diabetes.jax.org/Abraham, Kristin (NIH/NIDDK) [E]NoNoNo9/23/2013 4:21 PM

The NIDDK sponsored Type 1 Diabetes Resource (T1DR) at The Jackson Laboratory supports Type 1 Diabetes research by serving as an international repository for importation, curation, genotypic and phenotypic validation, cryopreservation, and distribution of mouse stocks of value to the scientific community.

Research Resources239
  
TRIGRDiabetesBiosamples; DatasetsClinical Research; Epidemiology; Interventional Trialhttp://trigr.epi.usf.edu/Akolkar, Beena (NIH/NIDDK) [E]NoNoNo9/23/2013 4:21 PM

This multi-center, international study, led by NICHD, has completed recruitment and is testing whether hydrolyzed infant formula compared to cow's milk-based formula decreases risk of developing type 1 diabetes in children with increased genetic susceptibility.  The last child was randomized to the study in February 2007.  All children will be observed until the age of 10 years, thus the final results of the study are expected to be available in year 2017.

Research Resources233
  
TODAYDiabetesComparative Effectiveness Research; Epidemiology; Health Disparities; Interventional Trial; Pediatrics; Racial Disparitieshttps://today.bsc.gwu.edu/web/today/home?p_p_id=58&p_p_lifecycle=0&_58_redirect=%2FLinder, Barbara (NIH/NIDDK) [E]NoNoNo9/23/2013 4:21 PM

The TODAY (Treatment Options for type 2 Diabetes in Adolescents and Youth) study demonstrated that type 2 diabetes in youth may have a more aggressive course than type 2 diabetes in adults. The TODAY cohort is being followed to describe the clinical course of type 2 diabetes that occurs at a young age, including the development of complications.

Research Resources211
  
SNAPNutrition; Digestive Disease; Pancreatic DiseaseBiosamplesClinical Research; Comparative Effectiveness Research; Interventional Trialhttp://www.snaptrial.org/Evans, Mary (NIH/NIDDK) [E]NoNoNo9/23/2013 4:14 PM

SNAP is a randomized multi-center clinical trial designed to test whether duodenojejunal (DJ) feeding is more effective than nasogastric (NG) feeding in providing enteral nutrition to patients with severe acute pancreatitis. SNAP will enroll participants with severe acute pancreatitis admitted to the intensive care unit. Upon enrollment, participants are assigned to NG or DJ feeding and managed for up to 28 days or until weaned on to solid food. Follow-up continues until participants are discharged from the hospital or for a maximum of 60 days. Outcomes relate to feeding tolerance and failure, nutritional status, risk for life-threatening pancreatic/systemic complications, and hospital mortality.

Research Resources231
  
SEARCHDiabetesEpidemiology; Health Disparities; Pediatrics; Racial Disparitieshttp://www.searchfordiabetes.org/Linder, Barbara (NIH/NIDDK) [E]NoNoNo9/23/2013 3:46 PM

SEARCH for Diabetes in Youth is a national multi-center study aimed at understanding more about diabetes among children and young adults in the United States. SEARCH Study centers are located in five states - South Carolina, Ohio, Colorado, California, and Washington. Some centers have various locations within each state. SEARCH is funded by the Centers for Disease and Prevention (CDC) and the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK).

Research Resources242
  
RISEDiabetesBiosamples; Protocols and Methods; Datasets; PhenotypingClinical Research; Ancillary Studieshttps://rise.bsc.gwu.edu/web/rise/home?p_p_id=58&p_p_lifecycle=0&_58_redirect=%2FSavage, Peter (NIH/NIDDK) [E]NoNoNo9/23/2013 3:40 PM

The RISE Consortium includes 3 studies each assessing the hypothesis that aggressive glucose lowering will lead to recovery of beta-cell function that will be sustained after treatment in those with prediabetes and early type 2 diabetes.

Research Resources209
  
PALFLiver DiseaseBiosamples; DNA; Tissues; DatasetsClinical Research; Interventional Trial; Pediatricshttp://www.palfstudy.org/Sherker, Averell (NIH/NIDDK) [E]NoNoNo9/23/2013 3:32 PM

This multi-center, multi-national collaborative group of pediatric clinical liver centers is aimed at identifying, characterizing, and developing management strategies for infants, children, and adolescents who present with acute liver failure (ALF). In addition to a database of pediatric patients with ALF, a clinical trial is being conducted to test whether the drug N-acetylcysteine (NAC) improves outcome (survival) for patients with ALF not caused by acetaminophen overdose.

Research Resources230
  
OPTNDiabetes; Digestive Disease; Endocrine Disease and Metabolic Disease; Hematologic Disease; Kidney Disease; Liver DiseaseDatasets; Protocols and Methodshttp://optn.transplant.hrsa.gov/Eggerman, Thomas (NIH/NIDDK) [E]NoNoNo9/23/2013 3:32 PM

The U.S. Organ Procurement and Transplantation Network (OPTN) maintains a registry of human tissues in order to ensure the success and efficiency of the U.S. organ transplant system.

Research Resources229
  
NURSADiabetes; Endocrine Disease and Metabolic Disease; Obesity; Liver Disease; Digestive DiseaseDatasets; Reagents; Protocols and Methods; Model SystemsSystems Biology; Genetics and Genomics; Cell Biology and Physiology; Imaging and Biotechnology; Immunology and Inflammationhttp://www.nursa.org/Margolis, Ronald (NIH/NIDDK) [E]NoNoNo9/23/2013 3:31 PM

The mission of NURSA is to accrue, develop, and communicate information that advances our understanding of the roles of nuclear receptors (NRs) in human diseases and conditions for which NRs play an integral role.

Research Resources208
  
NASH CRNLiver DiseaseBiosamples; Tissues; DNAClinical Research; Ancillary Studies; Interventional Trial; Pediatricshttps://jhuccs1.us/nash/http://www.nashcrn.comDoo, Edward (NIH/NIDDK) [E]NoNoNo9/23/2013 3:30 PM

The NASH CRN researches the nature and underlying cause of NASH and conducts clinical studies on prevention and treatment. Approximately 1,500 pediatric and adult participants throughout the United States and Canada with nonalcoholic fatty liver disease (NAFLD) have enrolled into a database which began in late 2003. The NASH CRN has recently reopened the database to enroll additional pediatric and adult participants with NAFLD. Serum, liver tissue, and genomic DNA samples are being collected and stored in the NIDDK repository for ongoing as well as future studies. A three-arm randomized, placebo-controlled clinical trial of pioglitazone versus vitamin E completed enrollment in 2009. In addition to this adult trial, a similar trial in pediatric NASH patients randomized 180 children to receive treatment with vitamin E, metformin, or placebo.

Research Resources252
  
Diabetes; Digestive Disease; Endocrine Disease and Metabolic Disease; Hematologic Disease; Kidney Disease; Liver Disease; Nutrition; Obesity; Pancreatic Disease; Urologic DiseaseBiomarkers; Biosamples; DNA; Tissues; Datasets; Model Systems; Animal Models; Cell Lines; Zebrafish; Protocols and Methods; Histology; Morphology; Phenotyping; Reagents; Antibodies; Primers; VectorsCell Biology and Physiology; Developmental Biology; Fibrosis; Pathobiology; Stem Cell Biology; Clinical Research; Ancillary Studies; Behavior; Biomarker Development; Comparative Effectiveness Research; Epidemiology; Health Disparities; Interventional Trial; Pediatrics; Racial Disparities; Translation; Transplantation; Women's Health; Genetics and Genomics; Imaging and Biotechnology; Immunology and Inflammation; Systems Biology; Bioinformatics; Biostatistics; Integrative biology; Omics; Pharmacogenomicshttp://commonfund.nih.gov/Smith, Philip (NIH/NIDDK) [E]NoNoNo9/23/2013 3:30 PM

The intent of NIH Common Fund is to provide a strategic and nimble approach to address key roadblocks in biomedical research that impede basic scientific discovery and its translation into improved human health. In addition, these programs capitalize on emerging opportunities to catalyze the rate of progress across multiple biomedical fields.  Common Fund programs are expected to transform the way a broad spectrum of health research is conducted. Initiatives that comprise Common Fund programs are intended to be catalytic in nature by providing limited term investments in strategic areas to stimulate further research through IC-funded mechanisms.

Research Resources255
  
MMRRCDiabetes; Digestive Disease; Endocrine Disease and Metabolic Disease; Hematologic Disease; Kidney Disease; Liver Disease; Nutrition; Obesity; Pancreatic Disease; Urologic DiseaseModel Systems; Tissues; DNA; Datasets; Animal Models; Protocols and Methods; Histology; Morphology; Phenotyping; ReagentsGenetics and Genomics; Cell Biology and Physiology; Developmental Biology; Stem Cell Biology; Pathobiology; Fibrosis; Imaging and Biotechnology; Immunology and Inflammation; Systems Biology; Bioinformatics; Biostatistics; Integrative biology; Omics; Pharmacogenomicshttp://www.mmrrc.org/Abraham, Kristin (NIH/NIDDK) [E]NoNoNo9/23/2013 3:26 PM

The MMRRC distributes and cryopreserves scientifically valuable, genetically engineered mouse strains and mouse ES cell lines with potential value for the genetics and biomedical research community. We are a national network of breeding and distribution facilities plus an information coordinating center serving together as NIH's premier repository of spontaneous and induced mutant mouse and cell lines.  Strains of mice are maintained in a cryopreserved state unless demand warrants that a live colony be established. Live mice are supplied from a production colony, from a colony recovered from cryopreservation, or via micro-injection of a cell line into host blastocysts. At its option, an MMRRC facility may offer cryopreserved material for resuscitation at the recipient scientist's institution. The MMRRC charges fees to partially cover repository costs.

Research Resources249
  
GUDMAPKidney Disease; Urologic DiseaseDatasets; Model Systems; Animal Models; Protocols and Methods; Histology; MorphologyGenetics and Genomics; Developmental Biology; Stem Cell Biology; Imaging and Biotechnology; Systems Biology; Bioinformatics; Omicshttp://www.gudmap.org/Hoshizaki, Deborah (NIH/NIDDK) [E]NoNoNo9/23/2013 3:26 PM

The GenitoUrinary Development Molecular Anatomy Project (GUDMAP) is a consortium of laboratories working to provide the scientific and medical community with tools to facilitate research. The key components are: (1) a molecular atlas of gene expression for the developing organs of the GenitoUrinary (GU) tract; (2) a high resolution molecular anatomy that highlights development of the GU system; (3) mouse strains to facilitate developmental and functional studies within the GU system; (4) tutorials describing GU organogenesis; and (5) rapid access to primary data via the GUDMAP database.

Research Resources228
  
MMPCDiabetes; Obesity; Endocrine Disease and Metabolic DiseaseModel Systems; Protocols and MethodsCell Biology and Physiologyhttp://www.mmpc.org/Laughlin, Maren (NIH/NIDDK) [E]NoNoNo9/23/2013 3:24 PM

The MMPC is a National Institutes of Health-sponsored resource that provides experimental testing services to scientists studying diabetes, obesity, diabetic complications, and other metabolic diseases in mice.

Research Resources226
  
dbMHCDiabetes; Digestive DiseaseDatasets; ReagentsClinical Researchhttp://www.ncbi.nlm.nih.gov/projects/gv/mhc/main.fcgi?cmd=initAkolkar, Beena (NIH/NIDDK) [E]NoNoNo9/23/2013 3:17 PM

The dbMHC database provides an open, publicly accessible platform for DNA and clinical data related to the human Major Histocompatibility Complex (MHC).

Research Resources200
  
HUSCLiver DiseaseBiosamplesAncillary Studies; Clinical Research; Interventional TrialDoo, Edward (NIH/NIDDK) [E]NoNoNo9/23/2013 3:11 PM

HUSC is a multi-center placebo-controlled trial of ursodiol in primary sclerosing cholangitis (PSC). A total of 150 patients with previously untreated PSC without cirrhosis were randomly assigned to receive high doses of ursodiol (20-25 mg/kg/day) or placebo for two years. Patients underwent medical evaluation, endoscopic retrograde cholangiography, and liver biopsy before randomization and again at two-year intervals. The endpoints of therapy were progression of hepatic fibrosis, liver decompensation, liver transplantation, or death. The treatment phase of the study was stopped for futility in June 2008.

Research Resources198
  
HBRNDigestive Disease; Liver DiseaseBiosamples; Tissues; DNAClinical Research; Ancillary Studies; Interventional Trial; Pediatricshttp://www.hepbnet.org/Doo, Edward (NIH/NIDDK) [E]NoNoNo9/23/2013 3:10 PM

The Hepatitis B Research Network (HBRN) brings together clinical centers with expertise in caring for patients with chronic hepatitis B virus (HBV) infection. An estimated 2 billion people worldwide have been infected with HBV and about 400 million persons are living with chronic HBV infection. Of those with childhood-acquired chronic HBV infection, it is estimated that 25% will later succumb to liver-related complications of cancer and cirrhosis if left untreated. The prevalence of HBV infection is uneven throughout the world, with significant burdens in Asia and the Pacific Islands, sub-Saharan Africa, the Amazon Basin, and Eastern Europe. The goal of the Network is to conduct research on chronic hepatitis B, in order to better understand the physiological effects of the disease and develop effective treatment strategies with the currently available therapies.

Research Resources241
  
GRADEDiabetesDatasets; Protocols and MethodsClinical Research; Ancillary Studieshttps://grade.bsc.gwu.edu/web/grade/homeLinder, Barbara (NIH/NIDDK) [E]NoNoNo9/23/2013 3:09 PM

GRADE will determine which combination of two medications is best for glycemic control in Type 2 Diabetes, has the fewest side effects, and is the most beneficial for overall health.

Research Resources196
  
FDTTDigestive DiseaseDatasetsClinical Research; Interventional TrialHamilton, Frank (NIH/NIDDK) [E]NoNoNo9/23/2013 2:57 PM

The FDTT study is a multi-center, randomized, placebo-controlled trial evaluating the tricyclic antidepressant, amitriptyline and the selective serotonin reuptake inhibitor (SSRI), escitalopram to placebo in patients with functional dyspepsia. The purpose of this study is to determine whether amitriptyline and escitalopram are more efficacious than placebo in relief of the symptoms of functional dyspepsia, adjusting for psychological and psychiatric co-morbidities.

Research Resources193
  
DILINDigestive Disease; Liver DiseaseBiosamples; Tissues; DNACell Biology and Physiology; Clinical Research; Ancillary Studies; Biomarker Development; Epidemiologyhttps://dilin.dcri.duke.edu/Serrano, Jose (NIH/NIDDK) [E]NoNoNo9/23/2013 2:55 PM

Both a prospective and retrospective database containing cases of drug-induced liver disease, DILIN is funded by a cooperative agreement and includes five clinical centers and a central data coordinating center. One of the goals of DILIN is to establish a database of well-characterized cases of drug-induced liver injury along with serum, DNA, and tissue samples that will facilitate research on the mechanisms of hepatic injury due to drugs. Cases of liver injury due to herbal medications are also included. DILIN will develop standardized definitions of drug-induced liver disease and standardization of scoring systems for causality.

Research Resources192
  
http://digestive.niddk.nih.gov/statistics/statistics.aspxEverhart, James (NIH/NIDDK) [V]NoNoNo9/23/2013 2:54 PM

A collection of statistics about specific digestive diseases, including prevalence, mortality, care delivery and cost.

Research Resources219
  
NGSPDiabetesProtocols and Methods; ReagentsClinical Researchhttp://www.ngsp.org/Akolkar, Beena (NIH/NIDDK) [E]NoNoNo9/23/2013 2:53 PM

The purpose of the NGSP is to standardize Hemoglobin A1c test results to those of the Diabetes Control and Complications Trial (DCCT) and United Kingdom Prospective Diabetes Study (UKPDS) which established the direct relationships between HbA1c levels and outcome risks in patients with diabetes.

Research Resources218
  
CSGADPDiabetes; Digestive DiseaseClinical Researchhttp://www.niaid.nih.gov/about/organization/dait/Pages/CSGADP.aspxAkolkar, Beena (NIH/NIDDK) [E]NoNoNo9/23/2013 2:53 PM

The Cooperative Study Group for Autoimmune Disease Prevention (CSGADP) was established in 2001 as a collaborative network of investigators with a focus on prevention of autoimmune disease, defined as halting the development of autoimmune disease prior to clinical onset by means other than global immunosuppression, and an emphasis on Type 1 diabetes.

Research Resources217
  
CITRDiabetesDatasetsTransplantationhttp://www.citregistry.org/Appel, Michael (NIH/NIDDK) [E]NoNoNo9/23/2013 2:52 PM

The mission of the Collaborative Islet Transplant Registry (CITR) is to expedite progress and promote safety in islet/beta cell transplantation through the collection, analysis, and communication of comprehensive and current data on all islet/beta cell transplants performed in North America, as well as some European and Australian centers.

Research Resources191
  
CORIDigestive DiseaseDatasetsClinical Research; Epidemiology; Bioinformaticshttp://www.cori.org/Serrano, Jose (NIH/NIDDK) [E]NoNoNo9/23/2013 2:52 PM

The Clinical Outcomes Research Initiative, CORI, provides gastrointestinal physicians, nurses and researchers with software, research data and tailor-made services aimed to advance the overall practice of endoscopy.

Research Resources240
  
CITCDiabetesTissues; BiosamplesClinical Researchhttp://www.citisletstudy.org/http://www.isletstudy.org/Eggerman, Thomas (NIH/NIDDK) [E]NoNoNo9/23/2013 2:51 PM

The Clinical Islet Transplantation (CIT) Consortium is a network of clinical centers and a data coordinating center established in 2004 to conduct studies of islet transplantation in patients with type 1 diabetes.

Research Resources190
  
ChiLDRENLiver DiseaseBiosamples; Tissues; DNA; DatasetsCell Biology and Physiology; Developmental Biology; Clinical Research; Ancillary Studies; Interventional Trial; Pediatrics; Transplantationhttp://www.childrennetwork.org/Sherker, Averell (NIH/NIDDK) [E]NoNoNo9/23/2013 2:51 PM

The overall goal of ChiLDREN is to establish a database of clinical information and serum and tissue samples from children across the United States and Canada with Biliary Atresia, Idiopathic Neonatal Hepatitis, Cystic Fibrosis Liver Disease, Alagille Syndrome, Alpha-1 Antitrypsin Deficiency, Bile Acid Synthesis Defects, Mitochondrial Hepatopathies, and Progressive Familial Intrahepatic Cholestasis in order to facilitate research and to perform clinical, epidemiological, and therapeutic trials in these important pediatric liver diseases. Three NIDDK-funded consortia, Biliary Atresia Research Consortium (BARC), Cholestatic Liver Disease Consortium (CLiC), and the Cystic Fibrosis Liver Disease (CFLD) Network were consolidated to form ChiLDREN.

Research Resources216
  
CIDRGenetics and Genomicshttp://www.cidr.jhmi.edu/McKeon, Catherine (NIH/NIDDK) [E]NoNoNo9/23/2013 2:49 PM

A centralized facility established to provide genotyping, sequencing and statistical genetics services for NIH-funded investigators seeking to identify genes that contribute to human disease.

Research Resources215
  
BISC (ImmPort)DiabetesDatasetsSystems Biologyhttps://immport.niaid.nih.gov/immportWeb/display.do?content=AboutImmPortSpain, Lisa (NIH/NIDDK) [E]NoNoNo9/23/2013 2:47 PM
The ImmPort system provides advanced information technology support in the production, analysis, archiving, and exchange of scientific data for the diverse community of life science researchers supported by NIAID/DAIT. It serves as a long-term, sustainable archive of data generated by investigators funded through the NIAID/DAIT. The core component of the ImmPort system is an extensive data warehouse containing an integration of experimental data supplied by NIAID/DAIT-funded investigators and genomic, proteomic, and other data relevant to the research of these programs extracted from a variety of public databases. The ImmPort system also provides data analysis tools and an immunology-focused ontology. The functionality of the ImmPort system will be expanded continuously over the life of the BISC contract to accommodate the needs of the NIAID/DAIT-funded research community. The analytical tools created and integrated as part of the BISC contract are available to any researcher within ImmPort after registration and approval by DAIT. Additionally, the data provided by NIAID/DAIT funded researchers in ImmPort will be available to all registered users after the appropriate embargo time.
Research Resources214
  
BCBCDiabetesAntibodies; Datasets; Model Systems; Protocols and Methods; ReagentsGenetics and Genomics; Cell Biology and Physiology; Imaging and Biotechnology; Systems Biology; Immunology and Inflammationhttp://www.betacell.org/Blondel, Olivier (NIH/NIDDK) [E]NoNoNo9/23/2013 2:47 PM
The mission of the BCBC is to facilitate interdisciplinary approaches that will advance our understanding of pancreatic islet cell development, regenerative capacity and function. The long-term goal is to develop a cell-based therapy, or treatments leading to controlled beta-cell renewal, in order to restore normal insulin production to diabetic patients.
Research Resources238
  
ACEsDiabetes; Digestive DiseaseDatasets; BiosamplesClinical Research; Interventional Trialhttp://www.autoimmunitycenters.org/Akolkar, Beena (NIH/NIDDK) [E]NoNoNo9/23/2013 2:46 PM
The objective of this initiative is to support integrated centers of basic, pre-clinical and clinical research in autoimmunity, emphasizing novel approaches and state-of-the-art technology to increase our understanding of the basic mechanisms of autoimmunity and self tolerance and to translate that information to the clinical setting.
Research Resources256
  
ASSESS-AKIKidney DiseaseBiomarkers; Biosamples; DNA; Tissues; Datasets; Protocols and Methods; PhenotypingGenetics and Genomics; Clinical Research; Ancillary Studies; Behavior; Biomarker Development; Epidemiology; Translation; Imaging and Biotechnology; Systems Biology; Bioinformatics; Biostatistics; Integrative biology; Omicshttps://assess-aki.hmc.psu.edu/Kimmel, Paul (NIH/NIDDK) [E]NoNoNo9/23/2013 2:45 PM
The ASSESS AKI recruits patients with and without an episode of AKI during a hospitalization, and follows them longitudinally for major cardiac, renal and mortality events.  An important aspect of the study is the prospective evaluation of potential biomarkers for renal and cardiac outcomes.
Research Resources247
  
Hematologic DiseaseDatasets; Cell LinesGenetics and Genomics; Systems Biology; Bioinformaticshttp://hembase.niddk.nih.gov/Miller, Jeff (NIH/NIDDK) [E]NoNoNo9/23/2013 2:43 PM
Hembase is an integrated browser and genome portal designed for web-based examination of the human erythroid transcriptome. To date, Hembase contains 15,752 entries from erythroblast Expressed Sequenced Tags (ESTs) and 380 referenced genes relevant for erythropoiesis. The database is organized to provide a cytogenetic band position, a unique name as well as a concise annotation for each entry. Search queries may be performed by name, keyword or cytogenetic location. Search results are linked to primary sequence data and three major human genome browsers for access to information considered current at the time of each search. Hembase provides interested scientists and clinical hematologists with a genome-based approach toward the study of erythroid biology.
Research Resources204
  
IBSOSDigestive DiseaseDatasetsClinical Research; Behavior; Interventional Trial; Women's Health; Imaging and BiotechnologyHamilton, Frank (NIH/NIDDK) [E]NoNoNo9/23/2013 2:34 PM
This multi-center clinical trial is designed to assess the short-term and long-term efficacy of cognitive behavior therapy (CBT) for irritable bowel syndrome (IBS) using two treatment delivery systems: self administered CBT and therapist administered CBT. Long term project goals are to develop an effective self-administered behavioral treatment program that can enhance the quality of patient care, improve clinical outcomes, and decrease the economic and personal costs of one of the most prevalent and intractable gastrointestinal disorders.
Research Resources225
  
IIDPDiabetesTissuesCell Biology and Physiologyhttp://iidp.coh.org/Default.aspxAppel, Michael (NIH/NIDDK) [E]NoNoNo9/23/2013 2:26 PM

The goal of the Integrated Islet Distribution Program (IIDP) is to work with the leading islet isolation centers in the U.S. to distribute high quality human islets to the diabetes research community, in order to advance scientific discoveries and translational medicine.

Research Resources207
  
LABSDigestive Disease; ObesityBiosamples; DatasetsClinical Research; Ancillary Studieshttp://www.edc.gsph.pitt.edu/labs/Horlick, Mary (NIH/NIDDK) [E]NoNoNo9/23/2013 2:18 PM

LABS is a consortium of six clinical centers and a data coordinating center conducting a prospective observational study of participants undergoing bariatric surgery.  Research staff, certified in standardized data collection procedures according to the protocol, collect data at pre-operative research visits, at surgery, 30 days post-operative, and at annual follow-up research visits at the 10 hospitals included in the six clinical centers.

Research Resources206
  
LTCDSDigestive Disease; Liver DiseaseBiosamples; TissuesCell Biology and Physiology; Ancillary Studies; Biomarker Development; Omicshttp://www.med.umn.edu/peds/gi/ltcds/Serrano, Jose (NIH/NIDDK) [E]NoNoNo9/23/2013 2:18 PM

The Liver Tissue Cell Distribution System (LTCDS) is a National Institutes of Health (NIH) service contract to provide human liver from regional centers for distribution to scientific investigators throughout the United States. These USA regional centers have active liver transplant programs with human subjects' approval to provide portions of the resected pathologic liver for which the transplant is performed. Frozen or fresh tissue is available from subcontractors for the usual forms of childhood and adult cirrhosis, fulminate liver failure, chronic rejection, and certain inborn errors of metabolism. “Normal” liver specimens may be requested, however, the supply is appropriately very limited and completion of large proposal requests is unlikely. A new service is now offered to provide isolated hepatocytes only to NIH investigators from "normal" human liver.

Research Resources254
  
KOMPDiabetes; Digestive Disease; Endocrine Disease and Metabolic Disease; Hematologic Disease; Kidney Disease; Liver Disease; Nutrition; Obesity; Pancreatic Disease; Urologic DiseaseModel Systems; Tissues; DNA; Datasets; Animal Models; Protocols and Methods; Histology; Morphology; Phenotyping; ReagentsGenetics and Genomics; Cell Biology and Physiology; Developmental Biology; Stem Cell Biology; Pathobiology; Fibrosis; Imaging and Biotechnology; Immunology and Inflammation; Systems Biology; Bioinformatics; Biostatistics; Integrative biology; Omics; Pharmacogenomicshttps://www.komp.org/Karp, Robert (NIH/NIDDK) [E]NoNoNo9/23/2013 2:14 PM

The Knockout Mouse Project (KOMP) is a trans-NIH initiative that aims to generate a comprehensive and public resource comprised of mouse embryonic stem (ES) cells containing a null mutation in every gene in the mouse genome.  Live knockout animals will be generated and characterized through comprehensive phenotyping.

Research Resources220
  
IASPDiabetesReagents; Protocols and Methods; AntibodiesClinical Researchhttp://www.immunologyofdiabetessociety.com/Akolkar, Beena (NIH/NIDDK) [E]NoNoNo9/23/2013 2:08 PM

The fundamental aim of IASP is to improve the measurements of the autoantibodies predictive of type 1 diabetes.

Research Resources224
  
ITNDiabetes; Digestive DiseaseDatasets; BiosamplesClinical Research; Interventional Trialhttp://www.immunetolerance.org/Akolkar, Beena (NIH/NIDDK) [E]NoNoNo9/23/2013 2:05 PM

The ITN is an international consortium of scientists and physicians dedicated to the clinical evaluation of novel tolerogenic approaches for the treatment of autoimmune diseases, asthma and allergic diseases, and the prevention of graft rejection.

Research Resources244
  
HNRIMNutritionhttp://hnrim.nih.gov/Krebs-Smith, James (NIH/NIDDK) [E]NoNoNo9/23/2013 2:05 PM

HNRIM is a searchable database of nutrition research and research training activities supported by the federal government and maintained by the NIH Division of Nutrition Research Coordination (DNRC). Human nutrition research is defined as research encompassing studies in five major areas: biomedical and behavioral sciences, food sciences, nutrition monitoring and surveillance, nutrition education, and impact of nutrition on intervention programs and socioeconomic factors. Information regarding trends in nutrition research, specific institutions and investigators involved in this research, or areas of agency emphases can be obtained from database searches or from published summary reports.  Data for the system is prepared and submitted by participating agencies, and is updated annually.

Research Resources188
  
Teen-LABSDigestive Disease; ObesityBiosamples; DatasetsClinical Research; Ancillary Studies; Behavior; Epidemiology; Pediatricshttp://www.cincinnatichildrens.org/research/divisions/t/teen-labs/default/Horlick, Mary (NIH/NIDDK) [E]NoNoNo9/23/2013 1:19 PM

The Teen-LABS consortium is made up of five clinical centers and a data coordinating center.  The goal of Teen-LABS is to conduct clinical, epidemiological, and behavioral research in adolescent bariatric surgery, through an observational prospective study protocol.  Teen-LABS is an ancillary study to LABS, an observational study of adult bariatric surgery.  Research staff, certified in standardized uniform data collection according to the protocol, collect data at pre-operative research visits, at surgery, 30 days and six months post-operative, and annual post-operative research visits at the five participating centers.