Mice with deficiency of G protein gamma3 are lean and have seizures.
Emerging evidence suggests that the gamma subunit composition of an individual G protein contributes to the specificity of the hundreds of known receptor signaling pathways. Among the twelve gamma subtypes, gamma3 is abundantly and widely expressed in the brain. To identify specific functions and associations for gamma3, 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 gamma3 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 gamma3, these phenotypic changes are associated with significant reductions in beta2 and alphai3 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 alphabetagamma subunit associations supports the notion that even closely related gamma subtypes, such as gamma3 and gamma7, perform unique functions in the context of the organism.
Geisinger Clinic, Weis Center for Research, 100 North Academy Ave., Danville, PA 17822, USA.
William F
WF
Schwindinger
Kathryn E
KE
Giger
Kelly S
KS
Betz
Anna M
AM
Stauffer
Elaine M
EM
Sunderlin
Laura J
LJ
Sim-Selley
Dana E
DE
Selley
Sarah K
SK
Bronson
Janet D
JD
Robishaw
D000262:Adenylyl Cyclases / Q000378:metabolism; D000273:Adipose Tissue; D000818:Animals; D001835:Body Weight; D001921:Brain / Q000378:metabolism; D005260:Female; D044387:GTP-Binding Protein beta Subunits / Q000378:metabolism; D044388:GTP-Binding Protein gamma Subunits / Q000235:genetics* / Q000378:metabolism*; D018390:Gene Targeting; D016244:Guanosine 5'-O-(3-Thiotriphosphate) / Q000378:metabolism; D020962:Heterotrimeric GTP-Binding Proteins / Q000235:genetics / Q000378:metabolism; D006801:Humans; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D010641:Phenotype; D012640:Seizures / Q000235:genetics* / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology
C115783:Bscl2 protein, mouse; D044387:GTP-Binding Protein beta Subunits; D044388:GTP-Binding Protein gamma Subunits; C115784:Gng3 protein, mouse; D016244:Guanosine 5'-O-(3-Thiotriphosphate); D020962:Heterotrimeric GTP-Binding Proteins; D000262:Adenylyl Cyclases