We took a two-step approach to identify novel genes with roles in alcohol behavior. First, we developed a list of candidate genes by analyzing ethanol-responsive loci in several microarray studies in mice and humans (Kerns et al., 2005, Liu et al., 2006, Mayfield et al., 2002, Mulligan et al., 2006). Second, we investigated the consequences of genetic manipulation of several of these genes on acute behavioral responses to alcohol in Drosophila, C. elegans and mice. Here, we report our studies on multiple members of the Chloride Intracellular Channel (Clic) family of genes and their effects on alcohol related behavior. CLICs are typically small proteins with single GST-CLIC domains at the N- and C-termini. CLICs have several proposed biochemical functions including intracellular chloride channel activity (Ashley, 2003), modulation of TGF-β or bone morphogenic protein (BMP) signaling (Shukla et al., 2009), and regulation of ryanodine receptors (Jalilian et al., 2008), 14-3-3 proteins (Suginta et al., 2001) and A-kinase anchoring proteins (Shanks et al., 2002). The Clic gene family is represented in mammals, flies and worms by six (Clic1–Clic6), one (Clic) and two
