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Behavioral and metabolic changes in mice lacking Gβ5‐R7 complex
Author(s) -
Wang Qiang,
Levay Konstantin,
Slepak Vladlen
Publication year - 2012
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.26.1_supplement.838.3
Subject(s) - insulin resistance , phenotype , endocrinology , knockout mouse , medicine , biology , endocrine system , metabolic syndrome , obesity , steatosis , protein subunit , pancreas , genetics , gene , hormone
Gβ5 is a unique G protein beta subunit that dimerizes with R7 family RGS proteins instead of Gγ. Gβ5:R7 association is essential for stability of their complex and so the knockout of Gβ5 causes degradation of the entire Gβ5‐R7 family. Here we analyze the phenotypes of Gβ5 knockout (KO) and heterozygotes (HET) animals. The KO mice are lean, resistant to high fat diet, hyperactive and have lower serum insulin. The HETs are also slightly more active than the WT, but surprisingly, display signs of metabolic syndrome: late‐onset obesity, insulin resistance and liver steatosis. Thus, even a partial reduction in Gβ5‐R7 level causes distinct phenotypes. The expression of Gβ5‐R7 complexes was thought to be restricted to the nervous system. To understand the mechanisms involved in the etiology of Gβ5 KO and HET phenotypes, we re‐examined expression of Gβ5 complex in peripheral tissues. We found that it is present in glands, including adrenal and pancreas, with subsequent analysis of endocrine cells with ablated Gβ5 provides novel insights into the role of this complex. This study was supported by U.S. National Institutes of Health (NIH) grants GM 060019 (V.Z.S).