Skip to main content
Log in

Genetic regulation of gene-specific mRNA by ethanolin vivo and its possible role in ethanol preference in a cross with RI lines in mice

  • Published:
Biochemical Genetics Aims and scope Submit manuscript

Abstract

Relative ethanol preference is a well-recognized phenotype in a number of species, including mice, but the molecular basis for this phenotype remains speculative. We generated novel recombinant inbred (RI) mouse lines from C57BL/6J (ethanol preferring) and BALB/c (ethanol avoiding) strains and evaluated the effect of ethanol feeding on the mRNA levels of three genes (Adh-1, Adh-2, andCas-1) of alcohol metabolism. Ethanol feeding affects the mRNA levels of all three genes in both a gene- and a genotype-specific manner. The effect of ethanol feeding onAhd-2 mRNA, in particular, is highly correlated with the relative ethanol acceptance of the genotypes. DNA sequencing of ∼500 bp of the 5′ upstream region of theAhd-2 gene has yielded identical sequence for the two strains and the genetically determined associated factors are hypothesized to be regulatory proteins. Quantitative trait locus analysis on the RI lines should lead to the molecular characterization and mapping of such gene-specific regulatory factors.

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

Access this article

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

Instant access to the full article PDF.

Similar content being viewed by others

References

  • Agarwal, D. P., Tobar-Rojas, L., Harada, S., and Goedde, H. W. (1983). Comparative study of erythrocyte ALDH in alcoholics and control subjects.Pharm. Biochem. Behav. 1889.

    Article  CAS  Google Scholar 

  • Bond, S. L., and Singh, S. M. (1990). Studies with cDNA probes on thein vivo effect of ethanol on expression of genes of alcohol metabolism.Alcohol Alcohol. 5385.

    Google Scholar 

  • Bond, S. L., and Singh, S. M. (1994). DNA sequence analysis of the cytosolic acetaldehyde dehydrogenase gene (Ahd-2) in mouse strains with variable ethanol preferences.Biochem. Med. Metab. Biol. 52155.

    Article  PubMed  CAS  Google Scholar 

  • Bond, S. L., Wigle, M., and Singh, S. M. (1991). Acetaldehyde dehydrogenase (Ahd-2) associated DNA polymorphism in mouse strains with variable ethanol preferences.Alcohol. Clin. Exp. Res. 15304.

    Article  PubMed  CAS  Google Scholar 

  • Ceci, J. D., Zheng, Y. W., and Felder, M. (1987). Molecular analysis of mouse alcohol dehydrogenase: Nucleotide sequence of theAdh-1 gene and genetic mapping of a related nucleotide sequence to chromosome 3.Gene 59171.

    Article  PubMed  CAS  Google Scholar 

  • Chomczynski, P., and Sacchi, N. (1987). Single step method of RNA isolation by acid guanidium thiocyanate-phenol-chloroform extraction.Anal. Biochem. 162156.

    Article  PubMed  CAS  Google Scholar 

  • Cloninger, C. R. (1987). Recent advances in family studies of alcoholism. In Goedde, H., and Agarwal, D. (eds.),Genetics and Alcoholism Alan R. Liss, New York, pp. 47–66.

    Google Scholar 

  • Cloninger, C. R., Bohman, M., and Sigvardson, S. (1981). Inheritance of alcohol abuse.Arch. Gen. Psychiatry 38861.

    PubMed  CAS  Google Scholar 

  • Cotton, N. S. (1979). The familial incidence of alcoholism: A review.J. Stud. Alcohol 4089.

    PubMed  CAS  Google Scholar 

  • Crabb, D. W., Edenberg, H. J., Borson, W. F., and Li, T. K. (1989). Genotypes for ALDH deficiency and alcohol sensitivity: The inactive ALDH2-2 allele is dominant.J. Clin. Invest. 83314.

    Article  PubMed  CAS  Google Scholar 

  • Crabbe, J. C., Belkamp, J. K., and Buck, K. J. (1994). Genetic animal models for alcohol and drug abuse.Science 2641715.

    PubMed  CAS  Google Scholar 

  • Crabbe, J. C., Kosobud, A., Young, E. R., and Janowsky, J. S. (1983). Polygenic and single-gene determination of response to ethanol in BXD/Ty recombinant inbred mouse strains.Neurobehav. Toxicol. Teratol. 5181.

    PubMed  CAS  Google Scholar 

  • Deitrich, R. (1990). Genetics of alcoholism: How do we find the answer and what do we do then?Alcohol Alcohol. 25571.

    PubMed  CAS  Google Scholar 

  • Edenberg, H. J., Zhang, K., Fong, K., Bosron, W. F., and Li, T. K. (1985). Cloning and sequencing of cDNA encoding the complete mouse liver alcohol dehydrogenase.Proc. Natl. Acad. Sci. USA 822262.

    PubMed  CAS  Google Scholar 

  • El-Hage, S., and Singh, S. M. (1989). Regulation of catalase-specific mRNA and its processing during development in mice.Dev. Genet. 10339.

    Article  PubMed  CAS  Google Scholar 

  • Enomoto, N., Takase, S., Yasuhara, M., and Takada, A. (1990). Acetaldehyde metabolism in different aldehyde dehydrogenase-2 genotypes.Alcohol. Clin. Exp. Res. 15141.

    Article  Google Scholar 

  • Festing, M. F. W. (1979).Inbred Strains in Biomedical Research Oxford University Press, New York.

    Google Scholar 

  • Fourney, R. M., Miakoshi, J., Day, R. S., and Paterson, M. C. (1987). Northern blotting: Efficient RNA staining and transfer.Focus 105.

    Google Scholar 

  • Goedde, H. W., and Agarwal, D. P. (1987). Polymorphism of aldehyde dehydrogenase and alcohol sensitivity.Enzyme 3729.

    PubMed  CAS  Google Scholar 

  • Goedde, H. W., and Agarwal, D. P. (1989).Alcoholism: Biomedical and Genetic Aspects Pergamon Press, Toronto.

    Google Scholar 

  • Goedde, H. W., Agarwal, D. P., and Harada, S. (1983). The role of alcohol dehydrogenase and aldehyde dehydrogenase isozymes in alcohol metabolism, alcohol sensitivity and alcoholism.Isozymes Curr. Top. Bio. Med. Res. 8175.

    CAS  Google Scholar 

  • Goedde, H. W., Harada, S., and Agarwal, D. P. (1979). Racial differences in alcohol sensitivity: A new hypothesis.Hum. Genet. 51331.

    Article  PubMed  CAS  Google Scholar 

  • Harada, S., Agarwal, D. P., Goedde, H. W., Tagaki, S., and Ishikawa, B. (1982). Possible protective role against alcoholism for aldehyde dehydrogenase isozyme deficiency in Japan.Lancet 2(8302):827.

    Article  PubMed  CAS  Google Scholar 

  • Higuchi, S., Matsushita, S., Imazeki, H., Kinoshita, T., Tagaki, S., and Kono, H. (1994). Aldehyde dehydrogenase genotypes in Japanese alcoholics.Lancet 343(8899):741.

    Article  PubMed  CAS  Google Scholar 

  • Holmes, R. S., Andrews, S. H., and Beechey, C. V. (1981). Genetic regulation of alcohol dehydrogenase C2 in the mouse. Developmental consequences of the temporal locus (Adh-3t) and positioning of Adh-3 on chromosome 3.Dev. Genet. 289.

    Article  CAS  Google Scholar 

  • Holmes, R. S., Duley, J. A., Algar, E. M., Mather, P. B., and Raut, U. K. (1986). Biochemical and genetic studies on enzymes of alcohol metabolism: The mouse as a model organism for human studies.Alcohol Alcohol. 2141.

    PubMed  CAS  Google Scholar 

  • Hrubec, Z., and Omenn, G. S. (1981). Evidence of genetic predisposition to alcoholic cirrhosis and psychosis; Twin concordance for alcoholism and its biological endpoints by zygosity among male veterans.Alcohol. Clin. Exp. Res. 5207.

    PubMed  CAS  Google Scholar 

  • Jenkins, W. J., Cakebread, K., and Palmer, K. R. (1984). Effect of alcohol consumption on hepatic aldehyde dehydrogenase activity in alcoholic patients.Lancet 1(8385):1048.

    Article  PubMed  CAS  Google Scholar 

  • Karp, R. W. (1994). Genetic studies in alcohol research.Am. J. Med. Genet. (Neuropsych. Genet.) 54304.

    Article  CAS  Google Scholar 

  • Lander, E. S., and Botstein, D. (1989). Mapping mendelian factors underlying quantitative traits using RFLP linkage maps.Genetics 121185.

    PubMed  CAS  Google Scholar 

  • Leiber, C. S., and DeCarli, L. (1982). The feeding of alcohol liquid diets: Two decades of application and 1982 update.Alcohol. Clin. Exp. Res. 6531.

    Google Scholar 

  • Leiber, C. S., and DeCarli, L. (1989). Liquid diet technique of ethanol administration: 1989 update.Alcohol Alcohol. 24197.

    Google Scholar 

  • Li, T. K., Lumeng, L., McBride, W., and Murphy, J. (1987). Rodent lines selected for factors affecting alcohol consumption.Alcohol Alcohol. Suppl. 191.

    PubMed  CAS  Google Scholar 

  • McClave, J., and Dietrich, F. (1985).Statistics 3rd ed., Dellen, San Francisco.

    Google Scholar 

  • McClearn, G. E., and Rodgers, D. A. (1959). Differences in alcohol preference among inbred strains of mice.Q. J. Stud. Alcohol. 20691.

    Google Scholar 

  • McClearn, G. E., and Rodgers, D. A. (1961). Genetic factors in alcohol preference of laboratory mice.J. Comp. Physiol. Psychol. 54116.

    Google Scholar 

  • Plomin, R., and McClearn, G. E. (1993). Quantitative trait loci analysis and alcohol-related behaviors.Behav. Genet. 23197.

    Article  PubMed  CAS  Google Scholar 

  • Reimer, D. L., Bailley, J., and Singh, S. M. (1994). Complete cDNA and 5′ genomic sequence and multilevel regulation of the mouse catalase gene.Genomics 21325.

    Article  PubMed  CAS  Google Scholar 

  • Rodgers, D. A. (1966). Factors underlying differences in alcohol preference among inbred strains of mice.Psychosom. Med. 28498.

    Google Scholar 

  • Rodriguez, L. A., Plomin, R., Blizard, D. A., Jones, B. C., and McClearn, G. E. (1994). Quantitative and molecular genetic analysis of alcohol-related behavior in the BXD recombinant inbred (RI) strains of mice.Alcohol. Clin. Exp. Res. 18450 (abstract).

    Article  Google Scholar 

  • Ronganoparut, P., and Weaver, S. (1991). Isolation and characterization of a cytosolic dehydrogenase encoding cDNA from mouse liver.Gene 101261.

    Article  Google Scholar 

  • Ryden, T. A., and Beemon, K. (1989). Avian retroviral long terminal repeats bind CCAAT/inhancer binding protein.Mol. Cell. Biol. 91155.

    PubMed  CAS  Google Scholar 

  • Schisler, N. J., and Singh, S. M. (1989). Effect of ethanolin-vivo on enzymes which detoxify oxygen free radicals.Free Rad. Biol. Med. 7117.

    Article  PubMed  CAS  Google Scholar 

  • Singh, S. M. (1986). Variability in the effect of alcohol on alcohol metabolizing enzymes may determine relative sensitivity to alcohols: A new hypothesis.Can. J. Genet. Cytol. 28789.

    PubMed  CAS  Google Scholar 

  • Sokal, R., and Rohlf, F. (1973).Introduction to Biostatistics, W. H. Freeman, San Francisco.

  • Stamatoyannopoulous, G., Chen, S. H., and Fukui, M. (1975). Liver alcohol dehydrogenase in Japanese: High population frequency of atypical form and its possible role in alcohol sensitivity.Am. J. Hum. Genet. 27789.

    Google Scholar 

  • Tanksley, S. D. (1993). Mapping polygenes.Annu. Rev. Genet. 27205.

    Article  PubMed  CAS  Google Scholar 

  • Thomas, M., Peters, T. J., and Halsall, S. (1982). Role of hepatic acetaldehyde dehydrogenase in alcoholics: Demonstration of persistent reduction of cytosolic activity in abstaining patients.Lancet 2(8307):1057.

    Article  PubMed  CAS  Google Scholar 

  • Wang, C. H., and Singh, S. M. (1984). Genetic considerations in the effects of ethanol in mice. II. Trans-acting inducibility regulator(s) affecting alcohol dehydrogenase activity.Biochem. Genet. 22158.

    Article  Google Scholar 

  • Wang, C. H., and Singh, S. M. (1985). Genetic considerations in the effects of ethanol in mice. I. Genotype-dependent alterations in alcohol dehydrogenase activity.Can. J. Genet. Cytol. 27158.

    PubMed  CAS  Google Scholar 

  • Wei, V. L., and Singh, S. M. (1988). Genetically determined response of hepatic aldehyde dehydrogenase activity to ethanol exposure may be associated with alcohol sensitivity in mouse genotypes.Alcohol. Clin. Exp. Res. 1239.

    Article  PubMed  CAS  Google Scholar 

  • Zhang, K., Bosron, W. F., and Edenberg, H. J. (1987). Structure of the mouseAdh-1 gene and identification of a deletion in a long alternating purine-pyrimidine sequence in the first intron of strains expressing low alcohol dehydrogenase activity.Gene 5727.

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Rights and permissions

Reprints and permissions

About this article

Cite this article

Tagliabracci, C.E., Singh, S.M. Genetic regulation of gene-specific mRNA by ethanolin vivo and its possible role in ethanol preference in a cross with RI lines in mice. Biochem Genet 34, 219–238 (1996). https://doi.org/10.1007/BF02407021

Download citation

  • Received:

  • Revised:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF02407021

Key words

Navigation