Genetic considerations in the effects of ethanol in mice. II. A trans-acting inducibility regulator(s) affecting alcohol dehydrogenase (ADH) activity.

The inducibility of alcohol dehydrogenase (ADH) has been recognized in different systems including maize, Drosophila, and mice. Our earlier results showed strain-specific ADH responses to chronic ethanol administration relative to matched littermate controls in mice. For this study we used two strains which showed "induction" (BALB/c and S.W.) and two strains which showed "repression" (C57BL/6J and 129/ReJ) to produce three sets of F1 hybrids and their reciprocals and one set (BALB/c X C57BL/6J) of recombinant inbred (RI) lines. The ADH properties of the resulting genotypes were again evaluated following 15% ethanol treatment in drinking water (2 weeks) in relation to their littermate matched controls in replicated trials. Our F1 results suggest complete dominance for induction over repression at the phenotypic level, and the two repressed strains showed complementation. No significant differences were observed in the reciprocal F1's and all pairs of a given genotype-treatment combination yielded consistent results. The 1:1 segregation of RI lines suggests a single gene difference for ADH inducibility between BALB/c and C57BL/6J. These findings suggest the presence of a trans-acting inducibility regulator(s) for ADH which may or may not represent a single locus. Variability for such regulatory elements may provide an explanation for the commonly observed individual differences in natural populations for response to alcohol including alcohol metabolism.