title: Targeted disruption of the melanocortin-4 receptor results in obesity in mice.
abstract: The melanocortin-4 receptor (MC4-R) is a G protein-coupled, seven-transmembrane receptor expressed in the brain. Inactivation of this receptor by gene targeting results in mice that develop a maturity onset obesity syndrome associated with hyperphagia, hyperinsulinemia, and hyperglycemia. This syndrome recapitulates several of the characteristic features of the agouti obesity syndrome, which results from ectopic expression of agouti protein, a pigmentation factor normally expressed in the skin. Our data identify a novel signaling pathway in the mouse for body weight regulation and support a model in which the primary mechanism by which agouti induces obesity is chronic antagonism of the MC4-R.
authors.affiliation: Millennium Pharmaceuticals, Inc., Cambridge, Massachusetts 02139, USA.
authors.forename: D
authors.initials: D
authors.lastname: Huszar
authors.forename: C A
authors.initials: CA
authors.lastname: Lynch
authors.forename: V
authors.initials: V
authors.lastname: Fairchild-Huntress
authors.forename: J H
authors.initials: JH
authors.lastname: Dunmore
authors.forename: Q
authors.initials: Q
authors.lastname: Fang
authors.forename: L R
authors.initials: LR
authors.lastname: Berkemeier
authors.forename: W
authors.initials: W
authors.lastname: Gu
authors.forename: R A
authors.initials: RA
authors.lastname: Kesterson
authors.forename: B A
authors.initials: BA
authors.lastname: Boston
authors.forename: R D
authors.initials: RD
authors.lastname: Cone
authors.forename: F J
authors.initials: FJ
authors.lastname: Smith
authors.forename: L A
authors.initials: LA
authors.lastname: Campfield
authors.forename: P
authors.initials: P
authors.lastname: Burn
authors.forename: F
authors.initials: F
authors.lastname: Lee
mesh_terms: D000818:Animals; D001786:Blood Glucose / Q000032:analysis; D001923:Brain Chemistry; D004195:Disease Models, Animal; D004435:Eating; D005260:Female; D015870:Gene Expression; D018390:Gene Targeting / Q000379:methods*; D006579:Heterozygote; D006720:Homozygote; D007328:Insulin / Q000097:blood; D020738:Leptin; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D008820:Mice, Obese; D009765:Obesity / Q000097:blood / Q000235:genetics*; D011333:Pro-Opiomelanocortin / Q000235:genetics; D011506:Proteins / Q000032:analysis; D012333:RNA, Messenger / Q000032:analysis; D044105:Receptor, Melanocortin, Type 4; D018000:Receptors, Peptide / Q000235:genetics / Q000502:physiology*; D015398:Signal Transduction; D015430:Weight Gain / Q000235:genetics
chemical_list: D001786:Blood Glucose; D007328:Insulin; D020738:Leptin; D011506:Proteins; D012333:RNA, Messenger; D044105:Receptor, Melanocortin, Type 4; D018000:Receptors, Peptide; D011333:Pro-Opiomelanocortin