Mouse model implicates GNB3 duplication in a childhood obesity syndrome.
Proc Natl Acad Sci U S A
; 110(37): 14990-4, 2013 Sep 10.
Article
em En
| MEDLINE
| ID: mdl-23980137
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 ß3 (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.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Duplicação Gênica
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Proteínas Heterotriméricas de Ligação ao GTP
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Obesidade Infantil
Idioma:
En
Ano de publicação:
2013
Tipo de documento:
Article