We have identified dAlk as a transcript regulated by Drosophila LIM-domain only (dLMO) using gene expression microarrays. Previous studies implicated dLmo and the mammalian homologs Lmo3 and Lmo4 in behavioral responses to alcohol and cocaine [18], [19], [20]. We therefore hypothesized that Alk function might also regulate behavioral responses to these drugs of abuse. Here, we provide data supporting this hypothesis using experimental approaches that test ethanol-related behaviors in flies, mice, and humans. We found that Alk regulates the acute sedating effect of ethanol in flies and mice as well as ethanol consumption in a binge-drinking model in mice. In humans, polymorphisms in ALK were found to be associated with a low level of response to alcohol in two measures, body sway and subjective high, two phenotypes that predict future AUDs [21], [22]. Together, these data suggest that ALK is a candidate gene predisposing individuals to a higher risk for developing AUDs.
