Mapping of a putative genetic locus determining ethanol intake in the mouse

In the mouse, there is evidence that a single genetic locus is a major determinant of differences in ethanol intake between some preferring and non-preferring inbred strains. In this report, we present evidence from two independent experiments indicating that this locus maps to chromosome 1 and that its expressed product is the abundant protein LTW-4 (a 28 kDa, pI 5.6 protein expressed in brain, liver and kidney). The genetic association was found using a panel of 14 polypeptides of mouse brain which were visualized by two-dimensional electrophoresis and which exhibit genetic variation in isoelectric point. Fifteen BXD recombinant inbred strains and the two parental strains were typed for these loci and also tested for ethanol acceptance. Strains exhibiting the basic allele showed significantly higher ethanol acceptance. When 19 distantly related inbred mouse strains were tested for ethanol acceptance and typed for LTW-4, it was again found that strains exhibiting the basic allele showed significantly higher ethanol acceptance.