A Homozygous Null Mutation Delineates the Role of the Melanocortin-4 Receptor in Humans

Journal of Clinical Endocrinology and Metabolism

Volumn 89, Issue 5, 2004, Pages 2028-2032

  Lubrano Berthelier, Cécile ^a   Le Stunff, Catherine ^b   Bougnères, Pierre ^b   Vaisse, Christian ^a,c  

^a UNIVERSITY OF CALIFORNIA   (United States)

^b HÔPITAL SAINT VINCENT DE PAUL   (France)

^c UNIVERSITY OF CALIFORNIA   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

C PEPTIDE; GENE PRODUCT; GLUCOSE; INSULIN; LEPTIN; MELANOCORTIN 4 RECEPTOR;

ADOLESCENT; ANOREXIA; BODY MASS; COHORT ANALYSIS; CONFERENCE PAPER; CONTROLLED STUDY; ENERGY BALANCE; ENZYME ACTIVITY; FEMALE; GENE; GENE FUNCTION; GENE MUTATION; GENOTYPE; HETEROZYGOSITY; HOMEOSTASIS; HOMOZYGOSITY; HORMONE ACTION; HUMAN; HYPERINSULINEMIA; LONG TERM CARE; MAJOR CLINICAL STUDY; MALE; MC4R GENE; MOLECULAR CLONING; NULL ALLELE; OBESITY; PEDIGREE; PRIORITY JOURNAL; PROTEIN FUNCTION; SCHOOL CHILD;

BODY WEIGHT; CHILD; FEMALE; GROWTH; HOMOZYGOTE; HUMANS; HYPERINSULINISM; HYPOTHALAMO-HYPOPHYSEAL SYSTEM; MALE; METABOLISM, INBORN ERRORS; MUTATION; PEDIGREE; PITUITARY-ADRENAL SYSTEM; RECEPTOR, MELANOCORTIN, TYPE 4; RECEPTORS, CELL SURFACE; THYROID GLAND;

EID: 2442436539     PISSN: 0021972X     EISSN: None     Source Type: Journal    
DOI: 10.1210/jc.2003-031993     Document Type: Conference Paper

References (14)

1. Schwartz MW, Woods SC, Porte Jr D, Seeley RJ, Baskin DG 2000 Central nervous system control of food intake. Nature 404:661-671
2. Gantz I, Miwa H, Konda Y, Shimoto Y, Tashiro T, Watson SJ, DelValle J, Yamada T 1993 Molecular cloning, expression, and gene localization of a fourth melanocortin receptor. J Biol Chem 268:15174-15179
3. Farooqi IS, Matarese G, Lord GM, Keogh JM, Lawrence E, Agwu C, Sanna V, Jebb SA, Perna F, Fontana S, Lechler RI, DePaoli AM, O'Rahilly S 2002 Beneficial effects of leptin on obesity, t cell hyporesponsiveness, and neuroendocrine/metabolic dysfunction of human congenital leptin deficiency. J Clin Invest 110:1093-1103
4. Clement K, Vaisse C, Lahlou N, Cabrol S, Pelloux V, Cassuto D, Gourmelen M, Dina C, Chambaz J, Lacorte JM, Basdevant A, Bougneres P, Lebouc Y, Froguel P, Guy-Grand B 1998 A mutation in the human leptin receptor gene causes obesity and pituitary dysfunction. Nature 392:398-401
5. Vaisse C, Clement K, Durand E, Hercberg S, Guy-Grand B, Froguel P 2000 Melanocortin-4 receptor mutations are a frequent and heterogeneous cause of morbid obesity. J Clin Invest 106:253-262
6. Dubern B, Clement K, Pelloux V, Froguel P, Girardet J, Guy-Grand B, Tounian P 2001 Mutational analysis of melanocortin-4 receptor, agouti-related protein, and α-melanocyte-stimulating hormone genes in severely obese children. J Pediatr 139:204-209
7. Lubrano-Berthelier C, Durand E, Dubern B, Shapiro A, Dazin P, Weill J, Ferron C, Froguel P, Vaisse C 2003 Intracellular retention is a common characteristic of childhood obesity-associated mc4r mutations. Hum Mol Genet 12:145-153
8. Farooqi IS, Keogh JM, Yeo GS, Lank EJ, Cheetham T, O'Rahilly S 2003 Clinical spectrum of obesity and mutations in the melanocortin 4 receptor gene. N Engl J Med 348:1085-1095
9. Hinney A, Hohmann S, Geller F, Vogel C, Hess C, Wermter AK, Brokamp B, Goldschmidt H, Siegfried W, Remschmidt H, Schafer H, Gudermann T, Hebebrand J 2003 Melanocortin-4 receptor gene: case-control study and transmission disequilibrium test confirm that functionally relevant mutations are compatible with a major gene effect for extreme obesity. J Clin Endocrinol Metab 88:4258-4267
10. Marsh DJ, Hollopeter G, Huszar D, Laufer R, Yagaloff KA, Fisher SL, Burn P, Palmiter RD 1999 Response of melanocortin-4 receptor-deficient mice to anorectic and orexigenic peptides. Nat Genet 21:119-122
11. Kim MS, Small CJ, Stanley SA, Morgan DG, Seal LJ, Kong WM, Edwards CM, Abusnana S, Sunter D, Ghatei MA, Bloom SR 2000 The central melanocortin system affects the hypothalamo-pituitary thyroid axis and may mediate the effect of leptin. J Clin Invest 105:1005-1011
12. Le Stunff C, Fallin D, Schork NJ, Bougneres P 2000 The insulin gene vntr is associated with fasting insulin levels and development of juvenile obesity. Nat Genet 26:444-446
13. Erickson JC, Hollopeter G, Palmiter RD 1996 Attenuation of the obesity syndrome of ob/ob mice by the loss of neuropeptide y. Science 274:1704-1707
14. Bates SH, Stearns WH, Dundon TA, Schubert M, Tso AW, Wang Y, Banks AS, Lavery HJ, Haq AK, Maratos-Flier E, Neel BG, Schwartz MW, Myers Jr MG 2003 Stat3 signalling is required for leptin regulation of energy balance but not reproduction. Nature 421:856-859