title: Knockout of G protein β5 impairs brain development and causes multiple neurologic abnormalities in mice.
abstract: Gβ5 is a divergent member of the signal-transducing G protein β subunit family encoded by GNB5 and expressed principally in brain and neuronal tissue. Among heterotrimeric Gβ isoforms, Gβ5 is unique in its ability to heterodimerize with members of the R7 subfamily of the regulator of G protein signaling proteins that contain G protein-γ like domains. Previous studies employing Gnb5 knockout (KO) mice have shown that Gβ5 is an essential stabilizer of such regulator of G protein signaling proteins and regulates the deactivation of retinal phototransduction and the proper functioning of retinal bipolar cells. However, little is known of the function of Gβ5 in the brain outside the visual system. We show here that mice lacking Gβ5 have a markedly abnormal neurologic phenotype that includes impaired development, tiptoe-walking, motor learning and coordination deficiencies, and hyperactivity. We further show that Gβ5-deficient mice have abnormalities of neuronal development in cerebellum and hippocampus. We find that the expression of both mRNA and protein from multiple neuronal genes is dysregulated in Gnb5 KO mice. Taken together with previous observations from Gnb5 KO mice, our findings suggest a model in which Gβ5 regulates dendritic arborization and/or synapse formation during development, in part by effects on gene expression.
authors: Metabolic Diseases Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland 20892-1752, USA.
authors: Jian-Hua
authors: JH
authors: Zhang
authors: Mritunjay
authors: M
authors: Pandey
authors: Erica M
authors: EM
authors: Seigneur
authors: Leelamma M
authors: LM
authors: Panicker
authors: Lily
authors: L
authors: Koo
authors: Owen M
authors: OM
authors: Schwartz
authors: Weiping
authors: W
authors: Chen
authors: Ching-Kang
authors: CK
authors: Chen
authors: William F
authors: WF
authors: Simonds
mesh_terms: D000015:Abnormalities, Multiple / Q000235:genetics* / Q000378:metabolism* / Q000503:physiopathology; D000818:Animals; D001921:Brain / Q000002:abnormalities* / Q000254:growth & development* / Q000378:metabolism; D002531:Cerebellum / Q000002:abnormalities* / Q000254:growth & development / Q000378:metabolism; D044387:GTP-Binding Protein beta Subunits / Q000172:deficiency* / Q000235:genetics / Q000502:physiology; D018507:Gene Expression Regulation, Developmental / Q000235:genetics*; D006624:Hippocampus / Q000002:abnormalities* / Q000254:growth & development / Q000378:metabolism; D051379:Mice; D057507:Mice, 129 Strain; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D010641:Phenotype
chemical_list: D044387:GTP-Binding Protein beta Subunits; C094668:Gnb5 protein, mouse