Mouse model to study metabolism.
Generation of a floxed Gnsa gene for the G-protein Gs alpha (Gsalpha) for the construction of conditional knockout mice.
The heterotrimeric G protein Gsalpha 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 Gsalpha had limited usefulness in trying to decipher the role of Gsalpha pathways in specific tissues since only heterozygotes were viable and could be analyzed. Analysis was further complicated by the fact that Gsalpha is imprinted expressed in many metabolically active tissues.
Gsalpha-floxed mice were generated so that the metabolic effects of Gsalpha deficiency could be examined in specific tissues. Exon1, which is specific for Gsalpha, was surrounded with loxP recombination sites. Liver-specific knockouts of Gsalpha were obtained by mating the Gsalpha-floxed mice with albumin promoter-Cre-transgenic mice. Gsalpha exon1 was efficiently deleted. These mice have been used successfully to generate other tissue-specfic Gsalpha knockout mice.