title: Mouse model implicates GNB3 duplication in a childhood obesity syndrome.
abstract: 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.
authors: Department of Human Genetics, Emory University School of Medicine, Atlanta, GA 30322.
authors: Ian S
authors: IS
authors: Goldlust
authors: Karen E
authors: KE
authors: Hermetz
authors: Lisa M
authors: LM
authors: Catalano
authors: Richard T
authors: RT
authors: Barfield
authors: Rebecca
authors: R
authors: Cozad
authors: Grace
authors: G
authors: Wynn
authors: Alev Cagla
authors: AC
authors: Ozdemir
authors: Karen N
authors: KN
authors: Conneely
authors: Jennifer G
authors: JG
authors: Mulle
authors: Shikha
authors: S
authors: Dharamrup
authors: Madhuri R
authors: MR
authors: Hegde
authors: Katherine H
authors: KH
authors: Kim
authors: Brad
authors: B
authors: Angle
authors: Alison
authors: A
authors: Colley
authors: Amy E
authors: AE
authors: Webb
authors: Erik C
authors: EC
authors: Thorland
authors: Jay W
authors: JW
authors: Ellison
authors: Jill A
authors: JA
authors: Rosenfeld
authors: Blake C
authors: BC
authors: Ballif
authors: Lisa G
authors: LG
authors: Shaffer
authors: Laurie A
authors: LA
authors: Demmer
authors: M Katharine
authors: MK
authors: Rudd
mesh_terms: D000293:Adolescent; D000328:Adult; D000818:Animals; D001921:Brain / Q000378:metabolism; D002648:Child; D002675:Child, Preschool; D002872:Chromosome Deletion; D002881:Chromosomes, Human, Pair 12 / Q000235:genetics; D002898:Chromosomes, Human, Pair 8 / Q000235:genetics; D004195:Disease Models, Animal; D005260:Female; D019204:GTP-Binding Proteins / Q000378:metabolism; D020440:Gene Duplication; D020962:Heterotrimeric GTP-Binding Proteins / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D063766:Pediatric Obesity / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D010375:Pedigree; D013577:Syndrome; D014178:Translocation, Genetic
chemical_list: C454420:G-protein beta3 subunit; D019204:GTP-Binding Proteins; D020962:Heterotrimeric GTP-Binding Proteins
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