Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Article
  • Published:

Identification of sex–specific quantitative trait loci controlling alcohol preference in C57BL/6 mice

Nature Genetics volume 13, pages 147–153 (1996)Cite this article

Abstract

Mice from various inbred strains consume alcoholic beverages at highly reproducible and strain–specific levels. While most mice consume alcohol in moderate amounts, C57BL/6J animals exhibit sustained oral ingestion of high levels of alcohol in the presence of competing water and food. We now report a genetic investigation of this phenotype as one potential model for alcoholism. An intercross–backcross breeding protocol was used to identify two recessive alcohol preference quantitative trait loci (QTLs) that are both sex–restricted in expression. A comparison of our results with those of an earlier morphine preference study argues against the hypothesis of a single unified phenotype defined by a preference for all euphoria–producing drugs.

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Similar content being viewed by others

References

  1. Devor, E.J. & Cloninger, C.R. Genetics of alcoholism. Anna. Rev. Genet. 23, 19–36 (1989).

    Article  CAS  Google Scholar 

  2. Begleiter, H. & Kissin, B., Genetics of Alcoholism. (Oxford University Press, New York, 1995).

    Google Scholar 

  3. Dietrich, W.F. et al. Genetic identification of Mom-1, a major modifier locus affecting Min-induced intestinal neoplasia in the mouse. Cell 75, 631–639 (1993).

    Article  CAS  PubMed  Google Scholar 

  4. Mock, B.A., Krall, M.M. & Dosik, J.K. Genetic mapping of tumor susceptibility genes involved in mouse plasmacytomagenesis. Proc. Natl. Acad. Sci. USA. 90, 9499–9505 (1993).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. Jacoby, R.F. et al. Genetic analysis of colon cancer susceptibility in mice. Genomics 22, 381–387 (1994).

    Article  CAS  PubMed  Google Scholar 

  6. Lee, G.-H., Bennett, L.M., Carabeo, R.A. & Drinkwater, N.R. Identification of hepatocarcinogen-resistance genes in DB/2Mice. Genetics 139, 387–395 (1995).

    CAS  PubMed  PubMed Central  Google Scholar 

  7. Nagase, H. et al. Distinct genetic loci control development of benign and malignant skin tumours in mice. Nature Genet. 10, 424–429 (1995).

    Article  CAS  PubMed  Google Scholar 

  8. Hilbert, P. et al. Chromosomal mapping of two genetic loci associated with blood-pressure regulation in hereditary hypertensive rats. Nature 353, 521–529 (1991).

    Article  CAS  PubMed  Google Scholar 

  9. Jacob, H.J. et al. Genetic mapping of a gene causing hypertension in the stroke-prone spontaneously hypertensive rat. Cell 67, 213–224 (1991).

    Article  CAS  PubMed  Google Scholar 

  10. De Sanctis, G.T. et al. Quantitative locus analysis of airway hyperresponsiveness in A/J and C57BL/6J mice. Nature Genet. 11, 150–154 (1995).

    Article  CAS  PubMed  Google Scholar 

  11. Hesselbrock, M.N. in The Genetics of Alcoholism (eds Begleiter, H. & Kissin, B.) 40–69 (Oxford University Press, New York, 1995).

    Google Scholar 

  12. McClearn, G.E. & Rodgers, D.A. Differences in alcohol preference among inbred strains of mice. Quart. J. Stud. Alcoh. 20, 691–695 (1959).

    Google Scholar 

  13. Crabbe, J. Genetic animal models in the study of alcoholism. Alcohol. Clin. Exp. Res. 13, 120–127 (1989).

    Article  CAS  PubMed  Google Scholar 

  14. Berrettini, W.H., Ferraro, T.N., Alexander, R.C., Buchberg, A.M. & Vogel, W.H. Quantitative trait loci mapping of three loci controlling morphine preference using inbred mouse strains. Alcohole Genef. 7, 54–58 (1994).

    CAS  Google Scholar 

  15. McClearn, G.E. & Rodgers, D.A. Genetic factors in alcohol preference of laboratory mice. J. Comp. Physiol. Psychol. 54, 116–119 (1961).

    Article  Google Scholar 

  16. Bond, S.L., Wigle, M.R. & Singh, S.M. Acetaldehyde dehydrogenase (Ahd-2)-associated DNA polymorphisms in mouse strains with variable ethanol preferences. Alcohol. Clin. Exp. Res. 15, 304–307 (1991).

    Article  CAS  PubMed  Google Scholar 

  17. Lumeng, L., Murphy, J.M., McBride, W.J. & Li, T.-K. in The Genetics of Alcoholism. (eds. Begleiter, H. & Kissin, B.) 165–201 (Oxford University Press, New York, 1995).

    Google Scholar 

  18. Plomin, R. & McClearn, G.E. Quantitative trait loci (QTL) analyses and alcohol-related behaviors. Behav. Genet. 23, 197–211 (1993).

    Article  CAS  PubMed  Google Scholar 

  19. Phillips, T.J., Crabbe, J.C., Metten, P. & Belknap, J. Localization of genes affecting alcohol drinking in mice. Alcohol. Clin. Exp. Res. 18, 931–941 (1994).

    Article  CAS  PubMed  Google Scholar 

  20. Rodriguez, L.A., Plomin, R., Blizard, D.A., Jones, B.C. & McClearn, G.E. Alcohol acceptance, preference, and sensitivity in mice II. Quantitative trait loci mapping analysis using BXD recombinant inbred strains. Alcohol. Clin. Exp. Res. 19, 367–373 (1995).

    Article  CAS  PubMed  Google Scholar 

  21. Silver, L.M., Concepts and Application. (Oxford University Press, New York, 1995).

    Google Scholar 

  22. Crabbe, J.C., Belknap, J.K. & Buck, K.J. Genetic animal models of alcohol and drug abuse. Science 264, 1715–1723 (1994).

    Article  CAS  PubMed  Google Scholar 

  23. Lander, E. & Kruglyak, L. Genetic dissection of complex traits: guidelines for interpreting and reporting results. Nature Genet. 11, 241–247 (1995).

    Article  CAS  PubMed  Google Scholar 

  24. Rodgers, D.A. & McClearn, G.E. Mouse strain differences in preference for various concentrations of alcohol. Quart. J. Stud. Alcoh. 23, 26–33 (1962).

    CAS  Google Scholar 

  25. Harada, S., Agarwal, D.P., Goedde, H.W., Tagaki, S. & Ishikawa, B. Possible protective role against alcoholism for aldehyde dehydrogenase deficiency in Japan. Lancet. 2, 827 (1982).

    Article  CAS  PubMed  Google Scholar 

  26. Thomasson, H.R., Edenberg, H.J., Crabb, D.W. & Al, E. Alcohol and aldehyde dehydrogenase genotypes and alcoholism in Chinese men. Am. J. Hum. Genet. 48, 677–681 (1991).

    CAS  PubMed  PubMed Central  Google Scholar 

  27. Thomasson, H.R., Crabb, D.W., Edenberg, H.J. & Li, T.-K. Alcohol and aldehyde dehydrogenase polymorphisms and alcoholism. Behav. Genet. 23, 131–136 (1993).

    Article  CAS  PubMed  Google Scholar 

  28. Rodriguez, LA., Plomin, R., Blizard, DA., Jones, B.C., McClearn, G.E. Alcohol acceptance, preference, and sensitivity in mice. I. Quantitative genetic analysis using BXD recombinant inbred strains. Alcohol. Clin. Exp. Res. 18, 1416–1422 (1994).

    Article  CAS  PubMed  Google Scholar 

  29. Plomin, R., McClearn, G.E., Gora-Maslak, G. & Neiderhiser, J.M. Use of recombinant inbred strains to detect quantitative trait loci associated with behavior. Behav Genet. 21, 99–116 (1991).

    Article  CAS  PubMed  Google Scholar 

  30. Hesselbrock, V.M. in The Genetics of Alcoholism (eds Begleiter, H. & Kissin, B.) 17–39 (Oxford University Press, New York, 1995).

    Google Scholar 

  31. Bohman, M., Sigvardsson, S. & Cloninger, C.R. Maternal inheritance of alcohol abuse: cross-fostering analysis of adopted women. Arch. Gen. Psych. 38, 965–969 (1981).

    Article  CAS  Google Scholar 

  32. Cattanach, B.M. & Kirk, M. Differential activity of maternally and paternally derived chromosome regions in mice. Nature 315, 469–498 (1985).

    Article  Google Scholar 

  33. McMahon, F.J., Stine, O.C., Meyers, D.A., Simpson, S.G. & DePaulo, J.R. Patterns of maternal transmission in bipolar affective disorder Am. J. Hum. Genet. 56, 1277–86 (1995).

    CAS  Google Scholar 

  34. Gregor, P. et al. Murine serotonin transporter: sequence and localization to Chromosome 11. Mammal. Genome. 4, 283–284 (1993).

    Article  CAS  Google Scholar 

  35. Schuckit, M.A. A clinical model of genetic influences in alcohol dependence. J. Stud. Alcohol. 55, 5–17 (1994).

    Article  CAS  PubMed  Google Scholar 

  36. Rausch, J.L., Monteiro, M.G. & Schuckit, M.A. Platlet serotonin uptake in men with family histories of alcoholism. Neuropsychopharmacology 4, 83–86 (1991).

    CAS  PubMed  Google Scholar 

  37. Alexander, R.C., Duda, J., Vogel, W. & Berrettini, W.H. Morphine and cocaine preference in inbred mice. Psychiat. Genet. 3, 33–37 (1993).

    Article  Google Scholar 

  38. Dietrich, W.F. & others. A genetic map of the mouse with 4,006 simple sequence length polymorphisms. Nature Genet. 7, 220–245 (1994).

    Article  CAS  PubMed  Google Scholar 

  39. Soller, M. & Brody, T. On the power of experimental designs for the detection of linkage between marker loci and quantitative loci in crosses between inbred lines. Theor. Appl. Genet. 47, 35–39 (1976).

    Article  CAS  PubMed  Google Scholar 

  40. Martinez, O. & Curnow, R.N. Estimating the locations and the sizes of the effects of quantitative trait loci using flanking markers. Theor. Appl. Genet. 85, 480–488 (1992).

    Article  CAS  PubMed  Google Scholar 

  41. Xu, S. A comment on the simple regression method of interval mapping. Genetics 141, 1657–1659 (1995).

    CAS  PubMed  PubMed Central  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Molecular Biology, Princeton University, Princeton, New Jersey, 08544-1014, USA

    Justine A. Melo, Jay Shendure, Kara Pociask & Lee M. Silver

Authors
  1. Justine A. Melo
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Jay Shendure
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Kara Pociask
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Lee M. Silver
    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

Melo, J., Shendure, J., Pociask, K. et al. Identification of sex–specific quantitative trait loci controlling alcohol preference in C57BL/6 mice. Nat Genet 13, 147–153 (1996). https://doi.org/10.1038/ng0696-147

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1038/ng0696-147

This article is cited by

Search

Advanced search

Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing