Gs Alpha LoxP (Gnas tm1Lsw) Mouse

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

The heterotrimeric G protein G_sα 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 G_sα had limited usefulness in trying to decipher the role of G_sα pathways in specific tissues since only heterozygotes were viable and could be analyzed. Analysis was further complicated by the fact that G_sα is imprinted expressed in many metabolically active tissues.

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

Publication

Increased glucose tolerance and reduced adiposity in the absence of fasting hypoglycemia in mice with liver-specific Gs alpha deficiency.

Chen M, Gavrilova O, Zhao WQ, Nguyen A, Lorenzo J, Shen L, Nackers L, Pack S, Jou W, Weinstein LS.

J Clin Invest (2005 Nov) 115(11):3217-27. Abstract/Full Text