Resource

Fgfr3 KO Mouse

Acronym: Mutant Mouse: Fgfr3 NIDDK Contact: tao@niddk.nih.gov Principal Investigator(s):

Description:

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.

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