Point mutations in the melanocortin-4 receptor cause variable obesity in mice

Mammalian Genome

Volumn 17, Issue 12, 2006, Pages 1162-1171

  Meehan, Thomas P ^a   Tabeta, Koichi ^b   Du, Xin ^b   Woodward, Lanette S ^a   Firozi, Karen ^a   Beutler, Bruce ^b   Justice, Monica J ^a  

^a BAYLOR COLLEGE OF MEDICINE   (United States)

^b SCRIPPS RESEARCH INSTITUTE   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

ALPHA INTERMEDIN; ALPHA INTERMEDIN DERIVATIVE; ETHYLNITROSOUREA; MELANOCORTIN 4 RECEPTOR; PROTEIN; PROTEIN L300P;

AMINO ACID SEQUENCE; AMINO ACID SUBSTITUTION; ANIMAL CELL; ANIMAL EXPERIMENT; ANIMAL MODEL; ARTICLE; CELL MEMBRANE; CELL STRAIN HEK293; CELL SURFACE; CELLULAR DISTRIBUTION; CONTROLLED STUDY; CORRELATION ANALYSIS; DISEASE SEVERITY; ENERGY EXPENDITURE; FATBOY GENE; FLOW CYTOMETRY; GENE; GENE ISOLATION; GENE MAPPING; GENETIC LINKAGE; HOMOZYGOSITY; HUMAN; HUMAN CELL; HYPERPHAGIA; IMMUNOFLUORESCENCE; MALE; MC4R GENE; MOUSE; MOUSE MUTANT; NONHUMAN; NULL ALLELE; OBESITY; PATHOGENESIS; PHENOTYPIC VARIATION; POINT MUTATION; PROTEIN EXPRESSION; PROTEIN LOCALIZATION; PROTEIN TRANSPORT; SIGNAL TRANSDUCTION; SOUTHBEACH GENE; WILD TYPE;

ALKYLATING AGENTS; ALPHA-MSH; AMINO ACID SUBSTITUTION; ANIMALS; BINDING, COMPETITIVE; CELL MEMBRANE; CELLS, CULTURED; CYCLIC AMP; ENERGY METABOLISM; ETHYLNITROSOUREA; FEMALE; FLOW CYTOMETRY; FLUORESCENT ANTIBODY TECHNIQUE; HOMOZYGOTE; HUMANS; KIDNEY; MALE; MICE; MICE, INBRED C57BL; OBESITY; POINT MUTATION; PROTEIN TRANSPORT; RECEPTOR, MELANOCORTIN, TYPE 4; RECEPTORS, CELL SURFACE; SIGNAL TRANSDUCTION;

EID: 33845503531     PISSN: 09388990     EISSN: 14321777     Source Type: Journal    
DOI: 10.1007/s00335-006-0073-z     Document Type: Article

References (25)

1. Albarado DC, McClaine J, Stephens JM, Mynatt RL, Ye J, et al. (2004) Impaired coordination of nutrient intake and substrate oxidation in melanocortin-4 receptor knockout mice. Endocrinology 145, 249-252
2. Balthasar N, Dalgaard LT, Lee CE, Yu J, Funahashi H, et al. (2005) Divergence of melanocortin pathways in the control of food intake and energy expenditure. Cell 123, 493-505
3. Carroll L, Voisey J, Van Daal A (2004) Mouse models of obesity. Clin Dermatol 22, 345-349
4. Ellacott KLJ, Cone RD (2004) The central melanocortin system and the integration of short- and long-term regulators of energy homeostasis. Recent Prog Horm Res 59, 395-408
5. Farooqi IS, Keogh JM, Yeo GSH, Lank EJ, Cheetham T, et al. (2003) Clinical spectrum of obesity and mutations in the melanocortin 4 receptor gene. N Engl J Med 348, 1085-1095
6. Gantz I, Miwa H, Konda Y, Shimoto Y, Tashiro T, et al. (1993) Molecular cloning, expression, and gene localization of a fourth melanocortin receptor. J Biol Chem 268, 15174-15179
7. Gao Z, Lei D, Welch J, Le K, Lin J, et al. (2003) Agonist-dependent internalization of the human melanocortin-4 receptors in human embryonic kidney 293 cells. J Pharmacol Exp Ther 307, 870-877
8. Grosse J, Tarnow P, Rompler H, Schneider B, Sedlmeier R, et al. (2006) N-ethyl-N-nitrosourea-based generation of mouse models for mutant G-protein-coupled receptors. Physiol Genomics 26, 209-217
9. Ho G, MacKenzie RG (1999) Functional characterization of mutations in melanocortin-4 receptor associated with human obesity. J Biol Chem 274, 35816-35822
10. Hoebe K, Du X, Georgel P, Janssen E, Tabeta K, et al. (2003) Identification of Lps2 as a key transducer of MyD88-independent TIR signalling. Nature 424, 743-748
11. Huszar D, Lynch CA, Fairchild-Huntress V, Dunmore JH, Fang Q, et al. (1997) Targeted disruption of the melanocortin-4 receptor results in obesity in mice. Cell 88, 131-141
12. Jequier E (2002) Leptin signaling, adiposity, and energy balance. Ann N Y Acad Sci 967, 379-388
13. Kile BT, Hentges KE, Clark AT, Nakamura H, Salinger AP, et al. (2003) Functional genetic analysis of mouse chromosome 11. Nature 425, 81-86
14. Lubrano-Berthelier C, Durand E, Dubern B, Shapiro A, Dazin P, et al. (2003) Intracellular retention is a common characteristic of childhood obesity-associated MC4R mutations. Hum Mol Genet 12, 145-153
15. Lubrano-Berthelier C, Dubern B, Lacorte J-M, Picard F, Shapiro A, et al. (2006) Melanocortin 4 receptor mutations in a large cohort of severely obese adults: prevalence, functional classification, genotype-phenotype relationship, and lack of association with binge eating. J Clin Endocrinol Metab 91, 1811-1818
16. Nijenhuis WA, Garner KM, van Rozen RJ, Adan RA (2003) Poor cell surface expression of human melanocortin-4 receptor mutations associated with obesity. J Biol Chem 278, 22939-22945
17. Schioth HB, Lagerstrom MC, Watanobe H, Jonsson L, Vergoni AV, et al. (2003) Functional role, structure, and evolution of the melanocortin-4 receptor. Ann N Y Acad Sci 994, 74-83
18. Shinyama H, Masuzaki H, Fang H, Flier JS (2003) Regulation of melanocortin-4 receptor signaling: agonist-mediated desensitization and internalization. Endocrinology 144, 1301-1314
19. Ste. Marie L, Miura GI, Marsh DJ, Yagaloff K, Palmiter RD (2000) A metabolic defect promotes obesity in mice lacking melanocortin-4 receptors. Proc Natl Acad Sci USA 97, 12339-12344
20. Sutton GM, Trevaskis JL, Hulver MW, McMillan RP, Markward NJ, et al. (2006) Diet-genotype interactions in the development of the obese, insulin-resistant phenotype of C57BL/6J mice lacking melanocortin-3 or -4 receptors. Endocrinology 147, 2183-2196
21. Tao YX (2005) Molecular mechanisms of the neural melanocortin receptor dysfunction in severe early onset obesity. Mol Cell Endocrinol 239, 1-14
22. Tao Y-X, Segaloff DL (2003) Functional characterization of melanocortin-4 receptor mutations associated with childhood obesity. Endocrinology 144, 4544-4551
23. Tao Y-X, Segaloff DL (2005) Functional analyses of melanocortin-4 receptor mutations identified from patients with binge eating disorder and nonobese or obese subjects. J Clin Endocrinol Metab 90, 5632-5638
24. Trevaskis JL, Butler AA (2005) Double leptin and melanocortin-4 receptor gene mutations have an additive effect on fat mass and are associated with reduced effects of leptin on weight loss and food intake. Endocrinology 146, 4257-4265
25. Yeo GS, Lank EJ, Farooqi IS, Keogh J, Challis BG, et al. (2003) Mutations in the human melanocortin-4 receptor gene associated with severe familial obesity disrupts receptor function through multiple molecular mechanisms. Hum Mol Genet 12, 561-574