| First Author | Goldlust IS | Year | 2013 |
| Journal | Proc Natl Acad Sci U S A | Volume | 110 |
| Issue | 37 | Pages | 14990-4 |
| PubMed ID | 23980137 | Mgi Jnum | J:201055 |
| Mgi Id | MGI:5510884 | Doi | 10.1073/pnas.1305999110 |
| Citation | Goldlust IS, et al. (2013) Mouse model implicates GNB3 duplication in a childhood obesity syndrome. Proc Natl Acad Sci U S A 110(37):14990-4 |
| abstractText | Obesity is a highly heritable condition and a risk factor for other diseases, including type 2 diabetes, cardiovascular disease, hypertension, and cancer. Recently, genomic copy number variation (CNV) has been implicated in cases of early onset obesity that may be comorbid with intellectual disability. Here, we describe a recurrent CNV that causes a syndrome associated with intellectual disability, seizures, macrocephaly, and obesity. This unbalanced chromosome translocation leads to duplication of over 100 genes on chromosome 12, including the obesity candidate gene G protein beta3 (GNB3). We generated a transgenic mouse model that carries an extra copy of GNB3, weighs significantly more than its wild-type littermates, and has excess intraabdominal fat accumulation. GNB3 is highly expressed in the brain, consistent with G-protein signaling involved in satiety and/or metabolism. These functional data connect GNB3 duplication and overexpression to elevated body mass index and provide evidence for a genetic syndrome caused by a recurrent CNV. |
