Targeted deletion of one or two copies of the Gbeta5 gene has distinct effects on body weight and behavior in mice

Abstract

We describe the phenotypes of mice that lack either one or two copies of the gene encoding G protein beta subunit G beta 5. Gβ5 is unique in that instead of Gγ subunits, it forms obligatory heterodimers with RGS proteins of R7 family (RGS6, RGS7, RGS9 and RGS11). The Gβ5 knockout (KO) animals are leaner than wild type (WT) and are resistant to high fat diet. Surprisingly, the heterozygotes (HET) display the opposite phenotype: they are about 15% heavier than the WT and by 35% heavier than the KO mice. This body weight increase is associated with adiposity and is accompanied by a mild insulin resistance. The second discovered phenotype was the increase in locomotor activity, which was less prevalent in the HET than the KO. The increased activity correlated with a higher level of catecholamines, implicating sympathetic system as a potential mechanism involved in etiology of this phenotype. Analysis of mRNA from hipothalami and prituitary glands of the KO and HET mice detected changes in expression of somatostatin and some other peptide hormones. Thus, we show that both haploid insufficiency and the knockout of Gβ5 can perturb hormone secretion and influence metabolism and behavior.