Mouse model implicates GNB3 duplication in a childhood obesity syndrome

Ian S. Goldlust, Karen E. Hermetz, Lisa M. Catalano, Richard T. Barfield, Rebecca Cozad, Grace Wynn, Alev Cagla Ozdemir, Karen N. Conneely, Jennifer G. Mulle, Shikha Dharamrup, Madhuri R. Hegde, Katherine H. Kim, Brad Angle, Alison Colley, Amy E. Webb, Erik C. Thorland, Jay W. Ellison, Jill A. Rosenfeld, Blake C. Ballif, Lisa G. ShafferLaurie A. Demmer, Beverly A. Searle, Sarah L. Wynn, M. Katharine Rudd*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

26 Scopus citations


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 β3 (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.

Original languageEnglish (US)
Pages (from-to)14990-14994
Number of pages5
JournalProceedings of the National Academy of Sciences of the United States of America
Issue number37
StatePublished - Sep 10 2013

ASJC Scopus subject areas

  • General


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