motifs (Fognani et al., 2002). There is also concordance between rodents and humans for a role of PKNOX2 in alcohol-related phenotypes. A massive brain transcriptome study of gene expression alterations in rodents that display an innate tendency for a high or low degree of alcohol preference found a correlation between PKNOX2 expression and preference (Mulligan et al., 2006). Of functional interest, multiple isoforms of PKNOX2 exist due to alternative splicing that generates cytoplasmic localized versions of PKNOX2 that bind actin monomers to regulate the actin cytoskeleton. (Haller et al., 2004). In this regard all three PKNOX2 SNPs are located within introns of the gene and thus may potentially facilitate alternative splicing to generate PKNOX2 actin-interacting isoforms. This hypothesis directly relates to an accumulating body of work that implicates regulation of the actin cytoskeleton in binge drinking, the neuroadaptations associated with alcohol dependence and the negative affective state associated with protracted abstinence (Moonat et al., 2011). In addition, a recent analysis in drosophila and humans found that Ras suppressor 1 (Rsu1), a regulator of the actin cytoskeleton, affects alcohol consumption across species (Ojelade et al., 2015). Rsu1 acts downstream of the integrin cell adhesion molecule and upstream of the Ras-related C3
