Mammalian Genome

, Volume 5, Issue 9, pp 546–552

Genetics of dietary obesity in AKR/JxSWR/J mice: segregation of the trait and identification of a linked locus on Chromosome 4

  • D. B. West
  • J. Waguespack
  • B. York
  • J. Goudey-Lefevre
  • R. A. Price
Original Contributions


We describe a new multiple gene mouse model of differential sensitivity to dietary obesity that provides a tool for dissecting the genetic basis for body composition and obesity. AKR/J and SWR/J male mice, as well as male progeny of intercrosses between these strains, were fed a high-fat diet for 12 weeks beginning at 5 weeks of age. Body weight and energy intake were assessed weekly. At the conclusion of the dietary manipulation, an adiposity index was calculated by dividing the weight of seven dissected adipose depots by the carcass weight. AKR/J mice had approximately sixfold greater adiposity than SWR/J mice. Examination of the segregation of the adiposity trait in the progeny of crosses between these strains indicates that the trait is determined by a minimum of one to four genetic loci and that there is significant dominance of the AKR/J genotype. A preliminary analysis with markers linked to the known mouse obesity genes ob, db, tub, and fat showed no linkage with these loci. However, a quantitative trait locus was found that maps distal to the db gene on Chromosome (Chr) 4. This locus has been designated dietary obese 1 or Do1.


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. Altman, P.L., Katz, D.D. (1979). Biological Handbooks III. Inbred and Genetically Defined Strains of Laboratory Animals, Part I, Mouse and Rat. (Bethesda, Md.: Fed. Am. Soc. Exp. Biol.), pp 157–211.Google Scholar
  2. Bahary, N., Leibel, R.L., Joseph, L., Friedman, J.M. (1990). Molecular mapping of the mouse db mutation. Proc. Natl. Acad. Sci. USA 87, 8642–8646.Google Scholar
  3. Bahary, N., Zorich, G., Pachter, J.E., Leibel, R.L., Friedman, J.M. (1991). Molecular genetic linkage maps of mouse chromosomes 4 and 6. Genomics 11, 33–47.Google Scholar
  4. Bray, G.A., York, D.A. (1971). Genetically transmitted obesity in rodents. Physiol. Rev. 51, 598–646.Google Scholar
  5. Cowley, D.E., Pomp, D., Atchley, W.R., Eisen, E.J., Hawkins-Brown, D. (1989). The impact of maternal uterine genotype on postnatal growth and adult body size in mice. Genetics 122, 193–203.Google Scholar
  6. Curb, D.J., Marcus, E.B. (1991). Body fat and obesity in Japanese Americans. Am. J. Clin. Nutr. 53, 1552S-1555S.Google Scholar
  7. Dietrich, W., Katz, H., Lincoln, S.E., Shin, H.S., Friedman, J., Dracopoli, N. Lander, E.S. (1992). A genetic map of the mouse suitable for typing intraspecific crosses. Genetics 131, 423–447.Google Scholar
  8. Dreon, D.M., Frey-Hewitt, B., Ellsworth, N., Williams, P.T., Terry, R.B., Wood, P.D. (1988). Dietary fat:carbohydrate ratio and obesity in middle-aged men. Am. J. Clin. Nutr. 47, 995–1000.Google Scholar
  9. Eberhart, G.P., West, D.B., Boozer, C.N., Atkinson, R.L. (1994). Insulin sensitivity of adipocytes from inbred mouse strains resistant or sensitive to diet-induced obesity. Am. J. Physiol., 266: R1423-R1428.Google Scholar
  10. Friedman, J.M., Leibel, R.L., Bahary, N. (1991). Molecular mapping of obesity genes. Mamm. Genome 1, 130–144.Google Scholar
  11. Hastings, I.M., Hill, W.G. (1989). A note on the effect of different selection criteria on carcass composition of mice. Anim. Prod. 48, 229–233.Google Scholar
  12. Kanarek, R.B., Hirsch, E. (1977). Dietary-induced overeating in experimental animals. Fed. Proc. 36(2), 154–158.Google Scholar
  13. Lander, E.S., Botstein, D. (1986a). Mapping complex genetic traits in humans: new methods using a complete RFLP linkage map. Cold Spring Harbor Symp. Quant. Biol. 51, 49–62.Google Scholar
  14. Lander, E.S., Botstein, D. (1986b). Strategies for studying heterogeneous genetic traits in humans by using a linkage map of restriction fragment length polymorphisms. Proc. Natl. Acad. Sci. USA 83, 7353–7357.Google Scholar
  15. Lander, E.S., Botstein, D. (1989). Mapping mendelian factors underlying quantitative traits using RFLP linkage maps. Genetics 121, 185–199.Google Scholar
  16. Marette, A., Richardson, J.M., Ramlal, T., Balon, T.W., Vranic, M., Pessin, J.E., Klip, A. (1992). Abundance, localization, and insulin-induced translocation of glucose transporters in red and white muscle. Am. J. Physiol. 263, C443-C452.Google Scholar
  17. Moll, P.P., Burns, T.L., Laver, R.M. (1991). The genetic and environmental sources of body mass index variability: the Muscatine ponderosity family study. Am. J. Hum. Genet. 49, 1243–1255.Google Scholar
  18. Pilch, P.F., Wilkinson, W., Garvey, W.T., Ciaraldi, T.P., Hueckstaedt, T.P., Olefsky, J.M. (1993). Insulin-responsive human adipocytes express two glucose transporter isoforms and target them to different vesicles. J. Clin. Endocrinol. Metab. 77, 286–289.Google Scholar
  19. Price, R.A., Ness, R., Laskarzewski, P. (1990). Common major gene inheritance of extreme overweight. Hum. Biol. 62, 747–765.Google Scholar
  20. Price, R.A., Charles, M.A., Pettitt, D.J., Knowler, W.C. (1993). Obesity in Pima-Indians: large increases among post World War II birth cohorts. Am. J. Phys. Anthropol. 92, 473–479.Google Scholar
  21. Rolls, B.J., Shide, D.J. (1992). The influence of dietary fat on food intake and body weight. Nutr. Rev. 50(10), 283–290.Google Scholar
  22. Schemmel, R., Mickelsen, O., Gill, J.L. (1976). Dietary obesity in rats: body weight and body fat accretion in seven strains of rats. J. Nutr. 100, 1041–1048.Google Scholar
  23. Sclafani, A. (1989). Dietary-induced overeating. Ann. N.Y. Acad. Sci. 575, 281–289.Google Scholar
  24. Sorenson, T.I.A., Price, R.A., Stunkard, A.J., Schulsinger, F. (1989). Genetics of obesity in adult adoptees and their biological siblings. Br. Med. J. 298, 87–90.Google Scholar
  25. West, D.B., Boozer, C.N., Moody, D.L., Atkinson, R.L. (1992). Dietary obesity in nine inbred mouse strains. Am. J. Physiol. 262, R1025-R1031.Google Scholar
  26. West, D.B., York, B.A., Goudey-Lefevre, J., Truett, G.E. (1994). Genetics and physiology of dietary obesity in the mouse. In: Pennington Center Nutrition Series, Vol. 5: Molecular and Genetic Aspects of Obesity, G.A. Bray, D. Ryan, eds., (Baton Rouge: Louisiana State University Press), in press.Google Scholar
  27. Wright, S. (1968). Evolution and the Genetics of Populations, Vol. 1. Genetic and Biometric Foundations. (Chicago: University of Chicago Press).Google Scholar

Copyright information

© Springer-Verlag New York Inc 1994

Authors and Affiliations

  • D. B. West
    • 1
  • J. Waguespack
    • 1
  • B. York
    • 1
  • J. Goudey-Lefevre
    • 1
  • R. A. Price
    • 2
  1. 1.Obesity, Diabetes and Metabolism Section, Pennington Biomedical Research CenterLouisiana State UniversityBaton RougeUSA
  2. 2.Behavioral Genetics Laboratory, Department of PsychiatryUniversity of PennsylvaniaPhiladelphiaUSA

Personalised recommendations