The role of the agouti gene in the yellow obese syndrome

Journal of Nutrition

Volumn 127, Issue 9, 1997, Pages

  Miltenberger, Rosalynn J ^a   Mynatt, Randall L ^a,c   Wilkinson, J Erby ^b   Woychik, Richard P ^a,d  

^a OAK RIDGE NATIONAL LABORATORY   (United States)

^b UNIVERSITY OF TENNESSEE   (United States)

^c PENNINGTON BIOMEDICAL RESEARCH CENTER   (United States)

^d CASE WESTERN RESERVE UNIVERSITY SCHOOL OF MEDICINE   (United States)

Author keywords

Agouti; Calcium; Melanocortin; Mouse; Obesity; Receptors

Indexed keywords

ACYL COENZYME A DESATURASE; ADENOSINE TRIPHOSPHATE; AGOUTI PROTEIN; ALPHA INTERMEDIN; AMINO ACID; BETA ACTIN; CALCIUM CHANNEL STIMULATING AGENT; COMPLEMENTARY DNA; CORTICOSTEROID; CYCLIC AMP; DNA; FATTY ACID SYNTHASE; GLUCOSE; GROWTH HORMONE; GROWTH HORMONE RELEASING FACTOR; GUANINE NUCLEOTIDE BINDING PROTEIN; HORMONE RECEPTOR; INSULIN; MELANIN; MESSENGER RNA; NEUROTOXIN; NUCLEOTIDE; PHOSPHOGLYCERATE KINASE; POTASSIUM; PROTEIN; RECOMBINANT PROTEIN; TRIACYLGLYCEROL; UNCLASSIFIED DRUG;

ADIPOSE TISSUE; BODY MASS; CALORIC INTAKE; CANCER SUSCEPTIBILITY; CONFERENCE PAPER; DIABETES MELLITUS; ENERGY EXPENDITURE; GENE; GENE EXPRESSION; HUMAN; HYPERINSULINEMIA; HYPOTHALAMUS; INSULIN RESISTANCE; MELANOCYTE; MOLECULAR CLONING; MUTATION; NONHUMAN; OBESITY; PHENOTYPE; SYNDROME; TRANSGENIC MOUSE;

AGOUTI; MUS MUSCULUS;

EID: 0030883353     PISSN: 00223166     EISSN: None     Source Type: Journal    
DOI: 10.1093/jn/127.9.1902s     Document Type: Conference Paper

References (81)

1. Ahmad, I., Finkelstein, J. A., Downs, T. R. & Frohman, L. A. (1993) Obesity-associated decrease in growth hormone-releasing hormone gene expression: a mechanism for reduced growth hormone mRNA levels in genetically obese Zucker rats. Neuroendocrinology 58: 332-337.
2. Ahmad, I., Steggles, A. W., Carrillo, A. J. & Finkelstein, J. A. (1989) Obesity-and sex-related alterations in growth hormone messenger RNA levels. Mol. Cell. Endocrinol. 65: 103-109.
3. hvy) mutation at the agouti locus. Genetics 142: 557-567.
4. Barsh, G. S. & Epstein, C. J. (1989a) The long-range restriction map surrounding the mouse agouti locus reveals a disparity between physical and genetic distances. Genomics 5: 9-18.
5. Barsh, G. S. & Epstein, C. J. (1989b) Physical and genetic characterization of a 75-kilobase deletion associated with a/, a recessive lethal allele at the mouse agouti locus. Genetics 121: 811-818.
6. Boston, B. A. & Cone, R. D. (1996) Characterization of melanocortin receptor subtype expression in murine adipose tissues and in the 3T3-L1 cell line. Endocrinology 137: 2043-2050.
7. Bray, G. A. (1996) Mechanisms for development of genetic, hypothalamic and dietary obesity. In: Pennington Center Nutrition Series (Bray, G. A. & Ryan, D. H., eds.), 1st ed., vol. 5, Molecular and Genetic Aspects of Obesity, pp. 3-66. Louisiana State University Press, Baton Rouge, LA.
8. Bray, G. A. & York, D. A. (1979) Hypothalamic and genetic obesity in experimental animals: an autonomie and endocrine hypothesis. Physiol. Rev. 59: 719-809.
9. Bultman, S. J., Russell, L. B., Gutierrez-Espeleta, G. A. & Woychik, R. P. (1991) Molecular characterization of a region of DNA associated with mutations at the agouti locus in the mouse. Proc Natl Acad. Sci. USA. 88: 8062-8066.
10. Bultman, S. J., Michaud, E. J. & Woychik, R. P. (1992) Molecular characterization of the mouse agouti locus. Cell 71: 1195-1204.
11. Coleman, D. L. & Burkart, D. L. (1977) Plasma corticosterone concentrations in diabetic (db) mice. Diabetologia 13: 25-26.
12. y) coat color mutation with an ecotropic murine leukemia virus genome. Proc. Natl. Acad. Sci. U.S.A. 80: 247-249.
13. Dickie, M. M. & Woolley, G. W. (1946) The age factor in weight of yellow mice. J. Hered. 37: 365-368.
14. Dubuc, P., Mobley, P.W.M. & Mahler, R. J. (1975) Elevated glucocorticoids in obese-hyperglycemic mice. Horm. Metab. Res. 7: 102.
15. y) mutation explained by deletion of a maternally expressed gene and the simultaneous production of agouti fusion RNAs. Development 120: 1695-1708.
16. Duhl, D. M., Vrieling, H., Miller, K. A., Wolff, G. L. & Barsh, G. S. (1994b) Neomorphic agouti mutations in obese yellow mice. Nat. Genet. 8: 59-65.
17. Fan, W., Boston, B. A., Kesterson, R. A., Hruby, V. J. & Cone, R. D. (1997) Role of melanocortinergic neurons in feeding and the agouti obesity syndrome. Nature (Lond.) 385: 165-168.
18. vy/A) (BALB/c X VY) F-1 hybrid mice by hyperglycemic peptide(s) from human pituitary glands. Endocrinology 113: 2097-2105.
19. vy/A and agouti A/a (BALB/c X VY) F1 hybrid mice to the same diets: glucose tolerance, weight gain, and adipocyte cellularity. Int. J. Obes. 12: 305-320.
20. Gantz, I., Konda, Y., Tashiro, T., Shimoto, Y., Miwa, H., Munzert, G., Watson, S. J., DelValle, J. & Yamada, T. (1993) Molecular cloning of a novel melanocortin receptor. J. Biol. Chem. 268: 8246-8250.
21. Gantz, I., Shimoto, Y., Konda, Y., Miwa, H., Dickinson, C. J. & Yamada, T. (1994) Molecular cloning, expression, and characterization of a fifth melanocortin receptor. Biochem. Biophys. Res. Commun. 200: 1214-1220.
22. Gill, A. M. & Yen, T. T. (1991) Effects of ciglitazone on endogenous plasma islet amyloid polypeptide and insulin sensitivity in obese-diabetic viable yellow mice. Life Sci. 48: 703-710.
23. Green, M. C. (1989) Catalogue of mutant genes and polymorphic loci. In: Genetic Variants and Strains of the Laboratory Mouse (Lyon, M. F. & Searle, A. G., eds.), pp. 17-20. Oxford University Press, Oxford, UK.
24. Griffon, N., Mignon, V., Facchinetti, P., Diaz, J., Schwartz, J. C. & Sokoloff, P. (1994) Molecular cloning of the rat fifth melanocortin receptor. Biochem. Biophys. Res. Commun. 200: 1007-1014.
25. Heston, W. E. & Vlahakis, G. (1962) Genetic obesity and neoplasia. J. Natl. Cancer Inst. 29: 197-209.
26. Hustad, C. M., Perry, W. L., Siracusa, L. D., Rasberry, C., Cobb, L., Cattanach, B. M., Kovatch, R., Copeland, N. G. & Jenkins, N. A. (1995) Molecular genetic characterization of six recessive viable alleles of the mouse agouti locus. Genetics 140: 255-265.
27. Huszar, D., Lynch, C. A., Fairchild-Huntress, V., Dunmore, J. H., Fang, Q., Berkemeier, L. R., Gu, W., Kesterson, R. A., Boston, B. A., Cone, R. D., Smith, F. J., Campfield, L. A., Burn, P. & Lee, F. (1997) Targeted disruption of the melanocortin-4 receptor results in obesity in mice. Cell 88: 131-141.
28. Jackson, E. J., Stolz, D. & Martin, R. (1976) Effect of adrenalectomy on weight gain and body composition of yellow obese mice (AVa). Horm. Metab. Res. 8: 452-455.
29. Jackson, I. J. (1994) Molecular and developmental genetics of mouse coat color. Annu. Rev. Genet. 28: 189-217.
30. Johnson, P. R. & Hirsch, J. (1972) Cellularity of adipose depots in six strains of genetically obese mice. J. Lipid Res. 13: 2-11.
31. Jones, B. H., Kim, J. H., Zemel, M. B., Woychik, R. P., Michaud, E. J., Wilkison, W.O. & Moustaid, N. (1996) Upregulation of adipocyte metabolism by agouti protein: possible paracrine actions in yellow mouse obesity. Am. J. Physiol. 270: E190-E192.
32. Kiefer, L. L., Ittop, O.R.R., Bunce, K., Truesdale, A. T., Willard, D. H., Nichols, J. S., Blanchard, S. G., Mountjoy, K., Chen, W.-J. & Wilkison, W. O. (1997) Mutations in the carboxyl terminus of the agouti protein decrease agouti inhibition of ligand binding to the melanocortin receptors. Biochemistry 36: 2084-2090.
33. Kim, J. H., Mynatt, R. L., Moore, J. W., Woychik, R. P., Moustaid, N. & Zemel, M. B. (1996) The effects of calcium channel blockade on agouti-induced obesity. FASEB J. 10: 1646-1652.
34. Klebig, M. L., Wilkinson, J. E., Geisler, J. G. & Woychik, R. P. (1995) Ectopic expression of the agouti gene in transgenic mice causes obesity, features of type Il diabetes, and yellow fur. Proc. Natl. Acad. Sci. U.S.A. 92: 4728-4732.
35. Kucera, G. T., Bortner, D. M. & Rosenberg, M. P. (1996) Overexpression of an Agouti cDNA in the skin of transgenic mice recapitulates dominant coat color phenotypes of spontaneous mutants. Dev. Biol. 173: 162-173.
36. Kwon, H. Y., Bultman, S. J., Loffler, C., Chen, W. J., Furdon, P. J., Powell, J. G., Usala, A. L., Wilkison, W., Hansmann, I. & Woychik, R. P. (1994) Molecular structure and chromosomal mapping of the human homolog of the agouti gene. Proc. Natl. Acad. Sci. U.S.A. 91: 9760-9764.
37. Labbe, O., Desamaud, F., Eggerickx, D., Vassart, G. & Parmentier, M. (1994) Molecular cloning of a mouse melanocortin 5 receptor gene widely expressed in peripheral tissues. Biochemistry 33: 4543-4549.
38. Lu, D., Willard, D., Patel, I. R., Kadwell, S., Overton, L., Kost, T., Luther, M., Chen, W., Woychik, R. P. & Wilkison, W. O. (1994) Agouti protein is an antagonist of the melanocyte-stimulating-hormone receptor. Nature (Lond.) 371: 799-802.
39. Mayer, T. C. & Fishbane, J. L. (1972) Mesoderm-ectoderm interaction in the production of the agouti pigmentation pattern in mice. Genetics 71: 297-303.
40. y) mutation. Proc. Natl. Acad. Sci. U.S.A. 91: 2562-2566.
41. y) is associated with the disruption of a novel RNA-binding protein. Genes Dev. 7: 1203-1213.
42. iapy) is correlated with methylation state and is influenced by parental lineage. Genes Dev. 8: 1463-1472.
43. Millar, S. E., Miller, M. W., Stevens, M. E. & Barsh, G. S. (1995) Expression and transgenic studies of the mouse agouti gene provide insight into the mechanisms by which mammalian coat color patterns are generated. Development 121: 3223-3232.
44. Miller, M. W., Duhl, D. M., Vrieling, H., Cordes, S. P., Ollmann, M. M., Winkes, B. M. & Barsh, G. S. (1993) Cloning of the mouse agouti gene predicts a secreted protein ubiquitously expressed in mice carrying the lethal yellow mutation. Genes Dev. 7: 454-467.
45. Mountjoy, K. G., Mortrud, M. T., Low, M. J., Simerly, R. B. & Cone, R. D. (1994) Localization of the melanocortin-4 receptor (MC4-R) in neuroendocrine and autonomic control circuits in the brain. Mol. Endocrinol. 8: 1298-1308.
46. Mountjoy, K. G., Robbins, L. S., Mortrud, M. T. & Cone, R. C. (1992) The cloning of a family of genes that encode the melanocortin receptors. Science (Washington, DC) 257: 543-546.
47. Mynatt, R. L., Miltenberger, R. J., Klebig, M. L., Zemel, M. B., Wilkinson, J. E., Wilkison, W. O. & Woychik, R. P. (1997) Combined effects of insulin treatment and adipose tissue-specific agouti expression on the development of obesity. Proc. Natl. Acad. Sci. U.S.A. 94: 919-922.
48. Olivera, B. M., Miljanich, G. P., Ramachandran, J. & Adams, M. E. (1994) Calcium channel diversity and neurotransmitter release. Annu. Rev. Biochem. 63: 823-867.
49. Perry, W. L., Hustad, C. M., Swing, D. A., Jenkins, N. A. & Copeland, N. G. (1995) A transgenic mouse assay for agouti protein activity. Genetics 140: 267-274.
50. Perry, W. L., Nakamura, T., Swing, D. A., Secrest, L., Eagleson, B., Hustad, C. M., Copeland, N. G. & Jenkins, N. A. (1996) Couple site-directed mutagenesis/ transgenesis identifies important functional domains of the mouse agouti protein. Genetics 144: 255-264.
51. Plocher, T. A. & Powley, T. L. (1976) Effect of hypophysectomy on weight gain and body composition in the genetically obese yellow (AVa) mouse. Metabolism 25: 593-602.
52. y) and nonagouti (a) coat color genes in the mouse. Dev. Biol. 42: 203-210.
53. Poole, T. W. (1975) Dermal-epidermal interactions and the action of alleles at the agouti locus in the mouse. Dev. Biol. 42: 203-210.
54. t) mice. J. Exp. Zool. 197: 115-119.
55. vy/a mice. Proc. Natl. Acad. Sci. U.S.A. 81: 2152-2156.
56. Roselli-Rehfuss, L., Mountjoy, K. G., Robbins, L. S., Mortrud, M. T., Low, M. J., Tatro, J. B., Entwistle, M. L., Simerly, R. B. & Cone, R. D. (1993) Identification of a receptor for gamma melanotropin and other proopiomelanocortin peptides in the hypothalamus and limbic system. Proc. Natl. Acad. Sci. U.S.A. 90: 8856-8860.
57. 1 hybrid mice. Proc. Soc. Exp. Biol. Med. 191: 408-419.
58. Shimizu, H., Shargill, N. S. & Bray, G. A. (1989) Adrenalectomy and response to corticosterone and MSH in the genetically obese yellow monse. Am. J. Physiol. 256: R494-R500.
59. Silvers, W. K. (1979) The Coat Colors of Mice: A Model for Mammalian Gene Action and Interaction. Springer-Verlag, New York, NY.
60. Silvers, W. K. & Russell, E. S. (1955) An experimental approach to action of genes at the agouti locus in the mouse. J. Exp. Zool. 130: 199-220.
61. Siracusa, L. D. (1991) Genomic organization and molecular genetics of the agouti locus in the mouse. Ann. N.Y. Acad. Sci. 642: 419-430.
62. Siracusa, L. D., Buchberg, A. M., Copeland, N. G. & Jenkins, N. A. (1989) Recombinant inbred strain and interspecific backcross analysis of molecular markers flanking the murine agouti coat color locus. Genetics 122: 669-679.
63. Siracusa, L. D., Russell, L. B., Jenkins, N. A. & Copeland, N. G. (1987) Allelic variation within the Emv-15 locus defines genomic sequences closely linked to the agouti locus on mouse chromosome 2. Genetics 117: 85-92.
64. Spiegslman, B. M. & Flier, J. S. (1996) Adipogenesis and obesity: rounding out the big picture. Cell 87: 377-389.
65. vy/-mice: relation to adult hyperinsulinemia and obesity. Proc. Soc. Exp. Biol. Med. 206: 145-151.
66. Weigle, D. S. & Kuijper, J. L. (1996) Obesity genes and the regulation of body fat content. BioEssays 18: 867-874.
67. Willard, D. H., Bodnar, W., Harris, C., Kiefer, L., Nichols, J. S., Blanchard, S., Hoffman, C., Moyer, M., Burkhart, W., Weiel, J. & Luther, M. A., Wilkison, W. O., Rocque, W. J. (1995) Agouti structure and function: characterization of a potent alpha-melanocyte stimulating hormone receptor antagonist. Biochemistry 34: 12341-12346.
68. Wilson, B. D., Ollmann, M. M., Kang, L., Stoffel, M., Bell, G. I. & Barsh, G. S. (1995) Structure and function of ASP, the human homolog of the mouse agouti gene. Human Mol. Genet. 4: 223-230.
69. ya) and non-yellow (aa) mice in parabiosis. Genetics 48: 1041-1058.
70. Wolff, G. L. (1965) Hereditary obesity and hormone deficiencies in yellow dwarf mice. Am. J. Physiol. 209: 632-636.
71. Wolff, G. L (1987) Body weight and cancer. Am. J. Clin. Nutr. 45: 168-180.
72. Wolff, G. L. & Flack, J. D. (1971) Genetic regulation of plasma corticosterone concentration and its response to castration and allogeneic tumour growth in the mouse. Nature N. Biol. 232: 181-182.
73. so) mutations. J. Hered. 69: 295-298.
74. vy/a) mice. The yellow mouse syndrome. J. Hered. 77: 151-158.
75. Woychik, R. P., Generoso, W. M., Russell, L. B., Cain, K. T., Cacheiro, N. L., Bultman, S. J., Selby, P. B., Dickinson, M. E., Hogan, B. L. & Rutledge, J. C. (1990) Molecular and genetic characterization of a radiation-induced structural rearrangement in mouse chromosome 2 causing mutations at the limb deformity and agouti loci. Proc. Natl. Acad. Sci. U.S.A. 87: 2588-2592.
76. Woychik, R. P., Stewart, T. A., Davis, L G., D'Eustachio, P. & Leder, P. (1985) An inherited limb deformity created by insertional mutagenesis in a transgenic mouse. Nature (Lond.) 318: 36-40.
77. vy/a mice. Biochim. Biophys. Acta 441: 213-220.
78. vy/-mice: ectopic expression of the agouti gene. FASEB J. 8: 479-488.
79. Yen, T. T., McKee, M. M. & Stamm, N. B. (1984) Thermogenesis and weight control. Int. J. Obes. 8 (Suppl. 1): 65-78.
80. 2+) results in stimulation of fatty acid synthase. Obes. Res. 3: 338s.
81. Zernel, M. B., Kim, J. H., Woychik, R. P., Michaud, E. J., Kadwell, S. H., Patel, I. R. & Wilkison, W. O. (1995b) Agouti regulation of intracellular calcium: role in the insulin resistance of viable yellow mice. Proc. Natl. Acad. Sci. U.S.A. 92: 4733-4737.