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

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, Ahd-2, and Cas-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 on Ahd-2 mRNA, in particular, is highly correlated with the relative ethanol acceptance of the genotypes. DNA sequencing of approximately 500 bp of the 5' upstream region of the Ahd-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.