Voluntary ethanol consumption by mice: genome-wide analysis of quantitative trait loci and their interactions in a C57BL/6ByJ x 129P3/J F2 intercross.

Consumption of ethanol solutions by rodents in two-bottle choice tests is a model to study human alcohol intake. Mice of the C57BL/6ByJ strain have higher ethanol preferences and intakes than do mice of the 129P3/J strain. F2 hybrids between these two strains were phenotyped using two-bottle tests involving a choice between water and either 3% or 10% ethanol. High ethanol preferences and intakes of the B6 mice were inherited as additive or dominant traits in the F2 generation. A genome screen using these F2 mice identified three significant linkages. Two loci, on distal chromosome 4 (Ap3q) and proximal chromosome 7 (Ap7q), strongly affected 10% ethanol intake and weakly affected 3% ethanol intake. A male-specific locus on proximal chromosome 8 (Ap8q) affected 3% ethanol preference, but not indexes of 10% ethanol consumption. In addition, six suggestive linkages (on chromosomes 2, 9, 12, 13, 17, and 18) affecting indexes of 3% and/or 10% ethanol consumption were detected. The loci with significant and suggestive linkages accounted for 35-44% of the genetic variation in ethanol consumption phenotypes. No additive-by-additive epistatic interactions were detected for the primary loci with significant and suggestive linkages. However, there were a few modifiers of the primary linkages and a number of interactions among unlinked loci. This demonstrates a significant role of the genetic background in the variation of ethanol consumption.