Morbid obesity resulting from inactivation of the ciliary protein CEP19 in humans and mice.
Am J Hum Genet
; 93(6): 1061-71, 2013 Dec 05.
Article
en En
| MEDLINE
| ID: mdl-24268657
ABSTRACT
Obesity is a major public health concern, and complementary research strategies have been directed toward the identification of the underlying causative gene mutations that affect the normal pathways and networks that regulate energy balance. Here, we describe an autosomal-recessive morbid-obesity syndrome and identify the disease-causing gene defect. The average body mass index of affected family members was 48.7 (range = 36.7-61.0), and all had features of the metabolic syndrome. Homozygosity mapping localized the disease locus to a region in 3q29; we designated this region the morbid obesity 1 (MO1) locus. Sequence analysis identified a homozygous nonsense mutation in CEP19, the gene encoding the ciliary protein CEP19, in all affected family members. CEP19 is highly conserved in vertebrates and invertebrates, is expressed in multiple tissues, and localizes to the centrosome and primary cilia. Homozygous Cep19-knockout mice were morbidly obese, hyperphagic, glucose intolerant, and insulin resistant. Thus, loss of the ciliary protein CEP19 in humans and mice causes morbid obesity and defines a target for investigating the molecular pathogenesis of this disease and potential treatments for obesity and malnutrition.
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Obesidad Mórbida
/
Proteínas de Ciclo Celular
/
Silenciador del Gen
Tipo de estudio:
Diagnostic_studies
/
Prognostic_studies
Límite:
Adult
/
Animals
/
Female
/
Humans
/
Male
Idioma:
En
Revista:
Am J Hum Genet
Año:
2013
Tipo del documento:
Article