Mice with Deficiency of G Protein γ3 Are Lean and Have Seizures

Abstract

Emerging evidence suggests that the γ subunit composition of an individual G protein contributes to the specificity of the hundreds of known receptor signaling pathways. Among the twelve γ subtypes, γ₃ is abundantly and widely expressed in the brain. To identify specific functions and associations for γ₃, a gene-targeting approach was used to produce mice lacking the Gng3 gene (Gng3^−/−). Confirming the efficacy and specificity of gene targeting, Gng3^−/− mice show no detectable expression of the Gng3 gene, but expression of the divergently transcribed Bscl2 gene is not affected. Suggesting unique roles for γ₃ in the brain, Gng3^−/− mice display increased susceptibility to seizures, reduced body weights, and decreased adiposity compared to their wild-type littermates. Predicting possible associations for γ₃, these phenotypic changes are associated with significant reductions in β₂ and α_i3 subunit levels in certain regions of the brain. The finding that the Gng3^−/− mice and the previously reported Gng7^−/− mice display distinct phenotypes and different αβγ subunit associations supports the notion that even closely related γ subtypes, such as γ₃ and γ₇, perform unique functions in the context of the organism.