Skip to main content
SpringerLink
Log in

Molecular mapping of obesity genes

  • Review
  • Published:
Mammalian Genome Aims and scope Submit manuscript

Abstract

Advances in molecular genetics have made it possible to clone mutant genes from mammals. This capability should facilitate efforts to determine the genetic factors that control food intake and body composition. In order to identify these genetic factors, we have been making use of mouse mutations that cause obesity. The basic premise of this approach is to take advantage of the mouse as a genetic system for the analysis of genetically complex disorders and to then apply that information to the study of human disease. This paper reviews: (1) current concepts concerning the control of body weight in man and other mammals; (2) the biologic characteristics of the mouse obesity mutations; (3) our progress in the use of positional cloning techniques to clone the mouse obese (ob) and diabetes (db) genes; (4) an approach to polygenic obesity in mice; and (5) the possible relevance of the mouse obesity mutations to human obesity.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  • Abbs, S., Roberts, R.G., Mathew, C.G., Bentley, D.R., and Bobrow, M.: Accurate assessment of intragenic recombination frequency within the Duchenne muscular dystrophy gene. Genomics 7: 602–606, 1990.

    Article  CAS  PubMed  Google Scholar 

  • Altman, P.L.: Inbred and Genetically Defined Strains of Laboratory Animals: Part I, Mouse and Rat, 16–20, Federation of American Societies for Experimental Biology, Bethesda MD, 1979.

    Google Scholar 

  • Arase, K., Shargill, N.S., and Bray, G.A.: Effects of corticotropin releasing factor on genetically obese (fatty) rats. Physiol Behav 45, 565–570, 1989.

    Article  CAS  PubMed  Google Scholar 

  • Bahary, N., Leibel, R.L., Joseph L., and Friedman, J.M.: Molecular mapping of the mouse db mutation. Proc Natl Acad Sci USA 87: 8642–8646, 1990.

    Article  CAS  PubMed  Google Scholar 

  • Balling, R., Deutsch, U., and Gruss, P: Undulated, a mutation affecting the development of the mouse skeleton, has a point mutation in the paired box of Pax-1. Cell 55: 531–535, 1988.

    Article  CAS  PubMed  Google Scholar 

  • Batt, R.A.: Decreased food intake in response to cholecystokinin (pancreozymin) in wild-type and obese mice (genotype oblob). Int J Obes 7: 25–29, 1983.

    CAS  PubMed  Google Scholar 

  • Begin-Heick, NL: Absence of the inhibitory effect of guanine nucleotides on adenylate cyclase activity in white adipocyte membranes of the oblob mouse: Effect of the ob gene. J Biol Chem 260: 6187–6193, 1985.

    CAS  PubMed  Google Scholar 

  • Bielschowsky, M., and Bielschowsky, F.: A new strain of mice with hereditary obesity. Proc Univ Otago M School 31: 29, 1953.

    Google Scholar 

  • Bjorkland, A., Hokfelt, T., and Swanson, L.W.: Integrated systems of the CNS, Part I. Hypothalamus, hippocampus, amygdala, retina. In Handbook of Chemical Neuroanatomy. Elsevier Press, New York, 1987.

    Google Scholar 

  • Bray, G.A.: An approach to control of food intake in humans. Med Clin N Amer 73: 29–45, 1989a.

    CAS  PubMed  Google Scholar 

  • Bray, G.A.: Genetic and hypothalamic mechanisms for obesity—finding the needle in the haystack. Am J Clin Nutr 50: 891–902, 1989b.

    CAS  PubMed  Google Scholar 

  • Bray, G.A., Shimomura, Y., Ohtake, M., and Walker, P.: Salivary gland weight and nerve growth factor in the genetically obese (oblob) mouse. Endocrinology 110: 47–50, 1982.

    Article  CAS  PubMed  Google Scholar 

  • Bray, G.A., York, D.A., and Fisler, J.S.: Experimental obesity: a homeostatic failure due to defective nutrient stimulation of the sympathetic nervous system. Vitamins and Hormones 45: 1–125, 1989.

    Article  CAS  PubMed  Google Scholar 

  • Brown, M.R., and Fisher, L.A.: Corticotropin-releasing factor: Effects on the autonomic nervous system and visceral systems. Federation Proc 44: 243–248, 1985.

    CAS  Google Scholar 

  • Brown, M.R., Fisher, L.A., Spiess, J., Rivier, C., Rivier, J., and Vale, W.: Corticotropin-releasing factor: Actions on the sympathetic nervous system and metabolism. Endocrinology 111: 928–931, 1982.

    Article  CAS  PubMed  Google Scholar 

  • Burke, D.T., Rossi, J.M., Leung, J., Koos, D.S., and Tilghman, S.M.: A mouse genomic library of yeast artificial chromosome clones. Mammalian Genome 1: 65, 1991.

    Article  CAS  PubMed  Google Scholar 

  • Camper, S.A., Saunders, T.L., Katz, R.W., and Reeves, R.H.: The Pit-1 transcription factor gene is a candidate for the murine snell dwarf mutation. Genomics 8: 586–590, 1990.

    Article  CAS  PubMed  Google Scholar 

  • Cebra-Thomas, J.A., Decker, C.L., Snyder, L.C., Pilder, S.H., and Silver, L.M.: Allele- and haploid-specific product generated by alternative splicing from a mouse t complex responder locus candidate. Nature 349: 239, 1991.

    Article  CAS  PubMed  Google Scholar 

  • Chabot, B., Stephenson, D.A., Chapman, V.M., Besmer, P., and Bernstein, A.: The protooncogene c-kit encoding a trasmembrane tyrosine kinase receptor maps to the mouse W locus. Nature 335: 88–89, 1988.

    Article  CAS  PubMed  Google Scholar 

  • Coleman, D.L.: Effects of parabiosis of obese with diabetes and normal mice. Diabetologid 9: 294–298, 1973.

    Article  CAS  Google Scholar 

  • Coleman, D.L.: Obese and diabetes: Two mutant genes causing diabetes-obesity syndromes in mice. Diabetologia 14: 141–148, 1978.

    Article  CAS  PubMed  Google Scholar 

  • Coleman, D.L.: Increased metablic efficiency in obese mutant mice. Intl J Obesity 9: 69–73, 1985.

    Google Scholar 

  • Coleman, D.L., and Eicher, E.M.: Fat (fat) and tubby (tub), two autosomal recessive mutations causing obesity syndromes in the mouse. J Heredity 81: 424–427, 1990.

    CAS  Google Scholar 

  • Coleman, D.L., and Hummel, K.P.: Hyperinsulinemia in preweaning diabetes (db) mice. Diabetologia 10: 607–610, 1974.

    Article  CAS  PubMed  Google Scholar 

  • Coleman, D.L., and Hummel, K.P.: Influence of genetic background on the expression of mutations at the diabetes locus in the mouse. II. Studies on background modifiers. Isr J Med 11: 708–718, 1975.

    CAS  Google Scholar 

  • Copeland, N.G., Gilbert, D.J., Cho, B.C., Donovan, P.J., Jenkins, N.A., Cosman, D., Anderson, D., Lyman, S.D., and Williams, D.E.: Mast cell growth factor maps near the Steel locus on mouse Chromosome 10 and is deleted in a number of Steel alleles. Cell 63: 175–183, 1990.

    Article  CAS  PubMed  Google Scholar 

  • D'Urso, M., Zucchi, I., Ciccodicola, A., Palmieri, G., Abidi, F.E., and Schlessinger, D.: Human glucose-6-phosphate dehydrogenase gene carried on a yeast artificial chromosome encodes active enzyme in monkey cells. Genomics 7: 531–534, 1990.

    Article  PubMed  Google Scholar 

  • Dickie, M.M., and Lane, P.W.: Mapping of the ob locus. Mouse News Lett 17: 52, 1957.

    Google Scholar 

  • Drumm, M.L., Smith, C.L., Dean, M., Cole, J.L., Iannuzzi, M.C., and Collins, F.S.: Physical mapping of the cystic fibrosis region by pulsed-field gel electrophoresis. Genomics 2: 346–354, 1988.

    Article  CAS  PubMed  Google Scholar 

  • Elvin, P., Slynn, G., Black, D., Graham, A., Butler, R., Anand, R., and Markham, A.F.: Isolation of cDNA clone using yeast artificial chromosome probes. Nucl Acids Res 18: 3913–3917, 1990.

    Article  CAS  PubMed  Google Scholar 

  • Fisher, E.M.C., Cavanna, J.S., and Brown, S.D.M.: Microdissection and microcloning of the mouse X Chromosome. Proc Natl Acad Sci USA 82: 5846–5849, 1985.

    Article  CAS  PubMed  Google Scholar 

  • Flatt, J.P.: Dietary fat, carbohydrate balance, and weight maintenance: Effects of exercise. Am J Clin Nutr 45: 296–306, 1987.

    CAS  PubMed  Google Scholar 

  • Fletcher, C., Norman, D.J., and Heintz, N.: Genetic mapping of meander tail, a mouse mutation affecting cerebellar development. Genomics, in press, 1991.

  • Foch, T.T., and McClearn, G.E.: Genetics, body weight and obesity. In A.J. Stunkard (ed.), Obesity, 48–71. Saunders, Philadelphia, 1980.

    Google Scholar 

  • Friedman, J.M., Leibel, R.L., Bahary, N. and Segal, D.A.: Molecular mapping of the mouse ob mutation. Submitted, 1991.

  • Frohman, L.A., and Bernardis, L.L.: Effect of hypothalamic stimulation on plasma glucose, insulin, and glucagon levels. Am J Physiol 221: 1596–1603, 1971.

    CAS  PubMed  Google Scholar 

  • Garthwaite, T.L., Martinson, D.R., Tseng, L.F., Hagen, T.C., and Menahan, L.A.: A longitudinal hormonal profile of the genetically obese mouse. Endocrinology 107: 671–676, 1980.

    Article  CAS  PubMed  Google Scholar 

  • Glaser, T., Rose, E., Morse, H., Housman, D., and Jones, C.: A panel of irradiation-reduced hybrids selectively retaining human Chromosome 11p13: Their structure and use to purify the WAGR gene complex. Genomics 6: 48–64, 1990.

    Article  CAS  PubMed  Google Scholar 

  • Green, E.D., and Olson, M.V.: Chromosomal region of the cystic fibrosis gene in yeast artificial chromosomes: A model for human genome mapping. Science 250: 94–98, 1990.

    Article  CAS  PubMed  Google Scholar 

  • Harris, R.B.S.: Role of set-point theory in regulation of body weight. FASEB J 4: 3310–3318, 1990.

    CAS  PubMed  Google Scholar 

  • Harris, R.B.S., Hervey, E., Hervey, G.R., and Tobin, G.: Body fat content in Zucker rats in parabiosis. J Physiol 312: 52, 1981.

    Google Scholar 

  • Herberg, L., and Coleman, D.L.: Laboratory animals exhibiting obesity and diabetes syndromes. Metabolism 26: 59, 1977.

    Article  CAS  PubMed  Google Scholar 

  • Herrmann, B.G.: Labeit, S., Poustka, A., King, T.R., and Lehrach, H.: Cloning of the T gene required in mesoderm formation in the mouse. Nature 343: 617–622, 1990.

    Article  CAS  PubMed  Google Scholar 

  • Hervey, G.R.: The effects of lesions in the hypothalamus in parabiotic rats. J Physiol 145: 336, 1959.

    CAS  PubMed  Google Scholar 

  • Hoebel, B.G.: Neurotransmitters in the control of feeding and its rewards: Manoanines, apiates and brain-gut peptides. In Eating and Its Disorders, 15–38, Raven Press, New York, 1984.

    Google Scholar 

  • Hummel, K.P., Coleman, D.L., and Lane, P.W.: The influence of genetic background on expression of mutations at the diabetes locus in the mouse. I. C57BL/KsJ and C57BL/6J strains. Biochem Genet 7: 1–3, 1972.

    Article  CAS  PubMed  Google Scholar 

  • Jeanrenaud, B.: An hypothesis on the aetiology of obesity: Dysfunction of the central nervous system as a primary cause. Diabetologia 28: 502–513, 1985.

    Article  CAS  PubMed  Google Scholar 

  • Johnson, P.R., Stern, J.S., Greenwood, M.R.C., Zucker, L.M., and Hirsch, J.: Effect of early nutrition on adipose cellularity and pancreatic insulin release in the Zucker rat. J Nutr 103: 738–743, 1973.

    CAS  PubMed  Google Scholar 

  • Keesey, R.E.: Physiological regulation of body weight and the issue of obesity. Med Clinics N Amer 73: 15–27, 1989.

    CAS  Google Scholar 

  • Keesey, R.E., and Pawley, T.L.: The regulation of body weight. Ann Rev Psychol 37: 109–133, 1986.

    Article  CAS  Google Scholar 

  • Knowler, W.C., Pettitt, D.J., Bennett P.H., and Williams, R.C.: Diabetes mellitus in the Pima Indians: Genetic and evolutionary considerations. Am J Phys Anthr 82: 107–114, 1983.

    Article  Google Scholar 

  • Lander, E.S., and Botstein, D.: Mapping Mendelian factors underlying quantitative traits using RFLP linkage maps. Genetics 121: 185–199, 1989.

    CAS  PubMed  Google Scholar 

  • Lane, P.W.: Mapping of the db locus. Mouse News Lett 38: 24, 1968.

    Google Scholar 

  • Larin, Z., Monaco, A.P., and Lehrach, H.: Yeast artificial chromosome libraries containing large inserts from mouse and human DNA. Proc Natl Acad Sci USA, in press, 1991.

  • Leibel, R.L., Bahary, N. and Friedman, J.M.: Genetic variation and nutrition in obesity: Approaches to the molecular genetics of obesity. In A.P. simopoulos and B. Childs (eds.); Genetic Variation and Nutrition, pp. 90–101, Kanger, Basel, 1990a.

    Google Scholar 

  • Leibel, R.L.: Is obesity due to a heritable difference in “set point” for adiposity? West J Med 153: 429–431, 1990b.

    CAS  PubMed  Google Scholar 

  • Leibel, R.L., Edens, N.K., and Fried, S.K.: Physiologic basis for the control of body fat distribution in humans. Ann Rev Nutr 9: 417–443, 1989.

    Article  CAS  Google Scholar 

  • Leibel, R.L., and Hirsch, J.: Diminished energy requirements in reduced-obese patients. Metabolism 33: 164–170, 1984.

    Article  CAS  PubMed  Google Scholar 

  • Leibowitz, S.F.: Brain monoamines and peptides: Roles in the control of eating behavior. Fed Proc 45: 1396–1403, 1986.

    CAS  PubMed  Google Scholar 

  • Leiter, E.H.: The influence of genetic background on expression of mutations at the diabetes locus in the mouse. IV. Male lethal syndrome in CBA/Lt mice. Diabetes 30: 1035–1044, 1981a.

    Article  CAS  PubMed  Google Scholar 

  • Leiter, E.H., Coleman, D.L., and Hummel, K.P.: The influence of genetic background on the expression of mutations at the diabetes locus in the mouse. III. Effect of H-2 haplotype and sex. Diabetes 30: 1029–1034, 1981b.

    Article  CAS  PubMed  Google Scholar 

  • Lyons, M.J., Faust, I.M., Hemmes, R.B., Buskirk, D.R., Hirsch, J., and Zabriskie, J.B.: A virally-induced obesity syndrome in mice. Science 216: 82–85, 1982.

    Article  CAS  PubMed  Google Scholar 

  • Mansour, S.L., Thomas, K.R., and Capecchi, M.R.: Disruption of the protooncogene Int-2 in mouse embryo-derived stem cells: A general strategy for targeting mutations to non-selectable genes. Nature 336: 348–352, 1988.

    Article  CAS  PubMed  Google Scholar 

  • Marshall, N.B., Barrnett, R.S., and Mayer, J.: Hypothalamic lesions in goldthioglucose injected mice. PSEBM 90: 240–244, 1955.

    CAS  Google Scholar 

  • Mayer, J., French, R.G., Zighera, C.F., and Barrnett, R.J.: Hypothalamic obesity in the mouse production, description and metabolic characteristics. Am J Physiol 182: 75–82, 1955.

    CAS  PubMed  Google Scholar 

  • Monaco, A.P., Neve, R.L., Colletti-Feener, C., Bertelson, C.J., Kurnit, D.M., and Kunkel, L.M.: Isolation of candidate cDNAs for portions of the Duchenne muscular dystrophy gene. Nature 323: 646–650, 1985.

    Article  Google Scholar 

  • Morley, J.: Neuropeptide regulation of appetite and weight. Endocrine Reviews 8: 256–286, 1987.

    Article  CAS  PubMed  Google Scholar 

  • Mrosovsky, N., and Powley, T.L.: Set points for body weight and fat. Behav Biol 20: 205–223, 1977.

    Article  CAS  PubMed  Google Scholar 

  • Nadeau, J.H.: Linkage and synteny homologies between mouse and man. Trends Genet 5: 82–86, 1990.

    Article  Google Scholar 

  • Paterson, A.H., Lander, E.S., Hewitt, J.D., Peterson, S., Lincoln, S.E., and Tanksley, S.D.: Resolution of quantitative traits into Mendelian factors by using a complete linkage map of restriction fragment length polymorphisms. Nature 335: 721, 1988.

    Article  CAS  PubMed  Google Scholar 

  • Pavan, W.J., Hieter, P., and Reeves, R.H.: Generation of deletion derivatives by targeted transformation of human-derived yeast artificial chromosomes. Proc Natl Acad Sci USA 87: 1300–1304, 1990.

    Article  CAS  PubMed  Google Scholar 

  • Prochazka, M., Leiter, E.H., and Serreze, D.V.: Three recessive loci required for insulin-dependent diabetes in nonobese diabetic mice. Science 237: 286–289, 1987.

    Article  CAS  PubMed  Google Scholar 

  • Ravelli, G.P., Stein, Z., and Susser, M.W.: Obesity in young men after famine exposure in utero and early infancy. N Engl J Med 295: 349–353, 1976.

    Article  CAS  PubMed  Google Scholar 

  • Ravussin, E., Abbott, W., Zawakzki, J.K., Young, A., Knowler, W.C., Jacobowitz, R., and Moll, P.P.: Familial dependence of the resting metabolic rate. N Engl J Med 315: 96–100, 1986.

    PubMed  Google Scholar 

  • Ravussin, E., Lillioja, S., Knowler, W.C., Dr., P.H., Christin, L., Freymond, D., Abbot, W.G.H., Boyce, V., Howard, B., and Bogardus, C.: Reduced rate of energy expenditure as a risk factor for body-weight gain. N Eng J Med 318: 467–472, 1988.

    Article  CAS  Google Scholar 

  • Readhead, C., Popko, B., Takahashi, N., David Shine, H., Saavedra, P.A., Sidman, R.L., and Hood, L.: Expression of a myelin basic protein gene in transgenic shiverer mice: Correction of the dysmyelinating phenotype. Cell 48: 703–712, 1987.

    Article  CAS  PubMed  Google Scholar 

  • Reeders, S.T., Keith, T., Green, P., Germino, G.G., Barton, N.J., Lehmann, O.J., Brown, V.A., Phipps, P., Morgan, J., Bear, J.C., and Parfrey, P.: Regional localization of the autosomal dominant polycyctic kidney disease locus. Genomics 3: 150–155, 1988.

    Article  CAS  PubMed  Google Scholar 

  • Reeves, R.H., Crowley, M.R., O'Hara, B.F., and Gearhart, J.D.: Sex, strain, and species differences affect recombination across an evolutionarily conserved segment of mouse Chromosome 16. Genomics 8: 141–148, 1990.

    Article  CAS  PubMed  Google Scholar 

  • Robert, B., Barton, P., Minty, A., Daubas, P., Weydert, A., Bonhomme, F., Catalan, J., Chazottes, D., Guénet, J.-L., and Buckingham, M.: Investigation of genetic linkage between myosin and actin genes using an interspecific mouse backcross. Nature 314: 181–183, 1985.

    Article  CAS  PubMed  Google Scholar 

  • Roberts, S.B., Savage, J., Coward, W.A., Chew, B., and Lucas, A.: Energy expenditure and intake in infants born to learn and overweight mothers. N Eng J Med 318: 461–466, 1988.

    Article  CAS  Google Scholar 

  • Robertson, E.J.: Pluripotent stem cell lines as a route into the mouse germ line. TIG (January): 9–13, 1986.

  • Rohner-Jeanrenaud, F., and Jeanrenaud, B.: A role for the vagus nerve in the etiology and maintenance of the hyperinsulinemia of genetically obese falfa rats. Intl J Obesity 9: 71–75, 1985.

    Google Scholar 

  • Rohner-Jeanrenaud, F., Walker, C.-L., Greco-Perotto, R., and Jeanrenaud, B.: Central corticotropin-releasing factor administration prevents the excessive body weight gain of genetically obese (falfa) rats. Endocrinology 124: 733–739, 1989.

    Article  CAS  PubMed  Google Scholar 

  • Rommens, J.M., Iannuzzi, M.C., Kerem, B., Drumm, M.L., Melmer, G., Dean, M., Rozmahel, R., Cole, J.L., Kennedy, D., Hidaka, N., Zsiga, M., Buchwald, M., Riordan, J.R., Tsui, L.-C., and Collins, F.S.: Identification of the cystic fibrosis gene: Chromosome walking and jumping. Science 245: 1059–1065, 1989.

    Article  CAS  PubMed  Google Scholar 

  • Rosen, B.S., Cook, K.S., Yaglom, J., Groves, D.L., Volanakis, J.E., Damm, D., White, T., and Spiegelman, B.M.: Adipsin and the alternative pathway of complement in the regulation of energy balance. In G.A. Bray, D. Ricquier, and B.M. Spiegelman (eds.); Obesity: Towards a Molecular Approach, 273–287, Wiley-Liss, New York, 1990.

    Google Scholar 

  • Rutman, R.J., Lewis, F.S., and Bloomer, W.D.: Bispiperidyl mustard, a new obesifying agent in the mouse. Science 153: 1000–1002, 1966.

    Article  CAS  PubMed  Google Scholar 

  • Sawchenko, P.E.: Evidence for a local site of action for glucocorticoids in inhibiting CRF and vasopressin expression in the paraventricular nucleus. Brain Res 403: 213–224, 1987.

    Article  CAS  PubMed  Google Scholar 

  • Scambler, P.J., Law, H.-Y., Williamson, R., and Cooper, C.S.: Chromosome mediated gene transfer of six DNA markers linked to the cystic fibrosis locus on human Chromosome 7. Nucl Acids Res 14: 7159–7174, 1986.

    Article  CAS  PubMed  Google Scholar 

  • Schlessinger, D.: Yeast artificial chromosomes: Tools for mapping and analysis of complex genomes. Trends Genet 6: 248–258, 1990.

    Article  CAS  PubMed  Google Scholar 

  • Shor-Posner, G., Azar, A.P., Insinga, S., and Leibowitz, S.F.: Deficits in the control of food intake after hypothalamic paraventricular nucleus lesions. Physiol Behavior 35: 883–890, 1985.

    Article  CAS  Google Scholar 

  • Silverman, G.A., Jockel, J.I., Domer, P.H., Mohr, R.M., Taillon-Miller, P., and Korsmeyer, S.J.: Yeast artificial chromosome cloning of a two-megabase-size contig within chromosomal band 18q21 established physical linkage between BCL2 and plasminogen activator inhibitor type-2. Genomics 9: 219–228, 1991.

    Article  CAS  PubMed  Google Scholar 

  • Sims, E.A., and Danforth, A.: Expenditure and storage of energy in man. J Clin Invest 79: 1019–1025, 1987.

    Article  CAS  PubMed  Google Scholar 

  • Smith, D.R., Smyth, A.P., and Moir, D.T.: Amplification of large artificial chromosomes. Proc Natl Acad Sci USA 87: 8242–8246, 1990a.

    Article  CAS  PubMed  Google Scholar 

  • Smith, G.P., Greenberg, D., Carp, E., and Gibbs, J.: Afferent information in the control of eating. In Obesity: Towards a Molecular Approach, 63–79, Wiley-Liss, New York, 1990b.

    Google Scholar 

  • Sorenson, T.I.A., Price, R.A., Stunkard, A.J., and Schulsinger, F.: Genetics of obesity in adult adoptess and their biological siblings. Br Med J 298: 87–90, 1989.

    Article  Google Scholar 

  • Stunkard, A.J., Harris, J.R., Pedersen, N.L., and McClearn, G.E.: The body-mass index of twins who have been reared apart. N Engl J Med 322: 1483–1487, 1990.

    Article  CAS  PubMed  Google Scholar 

  • Subhatme, P.V., and Margen, S.: Autoregulatory hemeostatic nature of energy balance. Am J Clin Nutr 35: 355–365, 1982.

    Google Scholar 

  • Thoday, J.M.: Location of polygenes. Nature 191: 368–370, 1961.

    Article  Google Scholar 

  • Tomita, T., Doull, V., Kimmel, J.R., and Pollock, H.G.: Pancreatic polypeptide and other hormones in pancreas of obese (oblob) mice. Diabetologia 27: 454–459, 1984.

    Article  CAS  PubMed  Google Scholar 

  • Tremblay, A., Poehlman, E.T., Nadeau, A., Dessault, J., and Bouchard, C.: Heredity and overfeeding-induced changes insubmaximal exercise VO2. J Appl Physiol 62: 539–544, 1987.

    CAS  PubMed  Google Scholar 

  • Truett, G.E., Bahary, N., Friedman, J.M., and Leibel, R.L.: The rat obesity gene fatty (fa) maps to Chromosome 5: Evidence for homology with mouse gene diabetes (db). Submitted, 1991.

  • Wallace, M.R., Marchuk, D.A., Andersen, L.B., Letcher, R., Odeh, H.M., Saulino, A.M., Fountain, J.W., Brereton, A., Nicholson, J., Mitchell, A.L., Brownstein, B.H., and Collins, F.S.: Type I neurofibromatosis gene: Identification of a large transcript disrupted in three NF1 patients. Science 249: 181–186, 1990.

    Article  CAS  PubMed  Google Scholar 

  • Weber, J.L., and May, P.E.: Abundant class of human DNA polymorphisms which can be typed using the polymerase chain reaction. Am J Hum Genet 44: 388–396, 1989.

    CAS  PubMed  Google Scholar 

  • Weigle, D.S.: Contribution of decreased body mass to diminished termic/effect of exercise in reduced-obese men. Int J Obesity 12: 567–578, 1988.

    CAS  Google Scholar 

  • White, R., and Lalowel, J.M.: Investigation of genetic linkage in human families. Adv Human Genet 16: 121–228, 1987.

    CAS  Google Scholar 

  • Wilson, B.E., Meyer, G.E., J.C. Cleveland, J., and Weigle, D.S.: Identification of candidate genes for a factor regulating body weight in primates. Am J Physiol, in press, 1991.

  • York, D.A., Marchinton, D., Holt, S.J., and Allars, J.: Regulation of sympathetic activity in lean and obese Zucker (falfa) rats. Am J Physiol 249: 1985.

Download references

Author information

Authors and Affiliations

  1. Howard Hughes Medical Institute, The Rockefeller University, 10021, New York, New York, USA

    Jeffrey M. Friedman

  2. Laboratory of Molecular Cell Biology, The Rockefeller University, 10021, New York, New York, USA

    Jeffrey M. Friedman & Nathan Bahary

  3. Laboratory of Human Behavior and Metabolism, The Rockefeller University, 10021, New York, New York, USA

    Rudolph L. Leibel

Authors
  1. Jeffrey M. Friedman
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Rudolph L. Leibel
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Nathan Bahary
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

About this article

Cite this article

Friedman, J.M., Leibel, R.L. & Bahary, N. Molecular mapping of obesity genes. Mammalian Genome 1, 130–144 (1991). https://doi.org/10.1007/BF00351059

Download citation

  • Received:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF00351059

Keywords

Search

Navigation