Gs Alpha LoxP (Gnas tm1Lsw) Mouse

Acronym: Mutant Mouse: GNAS (guanine nucleotide binding protein, alpha stimulating) NIDDK Contact: Principal Investigator(s): Lee Weinstein


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.

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