We observed phenotypic similarities between flies, mice, and humans in the acute response to alcohol as a function of genotype at the Alk locus. In the fruit fly, hypomorphic alleles of dAlk caused resistance to the motor incoordinating and sedating effects of ethanol. In mice, a polymorphism in Alk that is associated with low expression in the hippocampus also correlates with resistance to ethanol-induced ataxia. In humans, SNPs in ALK are associated with resistance to ethanol-induced ataxia as measured by body sway in response to an alcohol challenge. Insofar as motor-incoordinating behaviors related to ethanol can be compared between species, these results suggest that reduced Alk expression and/or function may result in resistance to the ataxic effect of ethanol. Interestingly, we found that AlkKO mice spent more time sedated in response to ethanol, suggesting that complete loss of Alk function leads to increased sensitivity to ethanol in this particular behavioral measure. The LORR test measures the length of time mice spend sedated and does not correlate with ethanol-induced ataxia in different strains of inbred mice [32]. Our data suggests that
