Mouse model implicates GNB3 duplication in a childhood obesity syndrome.

نویسندگان

  • 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 Shaffer
  • Laurie A Demmer
  • M Katharine Rudd
چکیده

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.

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عنوان ژورنال:
  • Proceedings of the National Academy of Sciences of the United States of America

دوره 110 37  شماره 

صفحات  -

تاریخ انتشار 2013