We hypothesized that Alk may regulate behavioral responses to ethanol in mammals since the expression of murine Alk is negatively regulated by LMO4 (Lasek et al., submitted) and Lmo3 and Lmo4 play roles in regulating ethanol and cocaine-related behaviors in mice [19], [20]. Using the databases available in GeneNetwork (www.genenetwork.org), we tested the genotype of BXD recombinant inbred (RI) strains at a polymorphic marker in the Alk locus, rs4137129, for associations with two types of measures: gene expression in specific brain regions and ethanol-related behaviors (see Materials and Methods for a description of the analysis). We identified three traits in BXD recombinant inbred mice that differed by genotype at the Alk locus and correlated with variation in Alk expression in at least one brain region. These traits were ethanol-induced ataxia [28] and two highly inter-correlated measures of ethanol drinking, preference and intake [29]. The genetic influence on these traits is shown as a heat-map for chromosome 17 (Figure 3A), which also depicts the location of the Alk locus and apparent Alk cis-regulation of expression in two brain regions, the hippocampus
