| First Author | Wang Q | Year | 2011 |
| Journal | FASEB J | Volume | 25 |
| Issue | 11 | Pages | 3949-57 |
| PubMed ID | 21804131 | Mgi Jnum | J:178414 |
| Mgi Id | MGI:5298313 | Doi | 10.1096/fj.11-190157 |
| Citation | Wang Q, et al. (2011) Targeted deletion of one or two copies of the G protein beta subunit Gbeta5 gene has distinct effects on body weight and behavior in mice. FASEB J 25(11):3949-57 |
| abstractText | We investigated the physiological role of Gbeta5, a unique G protein beta subunit that dimerizes with regulators of G protein signaling (RGS) proteins of the R7 family instead of Ggamma. Gbeta5 is essential for stability of these complexes, so that its knockout (KO)causes degradation of the entire Gbeta5-R7 family. We report that the Gbeta5-KO mice remain leaner than the wild type (WT) throughout their lifetime and are resistant to a high-fat diet. They have a 5-fold increase in locomotor activity, increased thermogenesis, and lower serum insulin, all of which correlate with a higher level of secreted epinephrine. Heterozygous (HET) mice are 2-fold more active than WT mice. Surprisingly, with respect to body weight, the HET mice display a phenotype opposite to that of the KO mice: by the age of 6 mo, they are >/= 15% heavier than the WT and have increased adiposity, insulin resistance, and liver steatosis. These changes occur in HET mice fed a normal diet and without apparent hyperphagia, mimicking basic characteristics of human metabolic syndrome. We conclude that even a partial reduction in Gbeta5-R7 level can perturb normal animal metabolism and behavior. Our data on Gbeta5 haploinsufficient mice may explain earlier observations of genetic linkage between R7 family mutations and obesity in humans. |
