The Clic family of genes has been implicated in a number of different biological processes or molecular functions (Maeda et al., 2008, Shukla et al., 2009, Singh & Ashley, 2007, Suh et al., 2004, Ulmasov et al., 2009). Many of these functions, however, remain largely unconfirmed or poorly characterized. As a non-biased analysis of possible mechanisms for Clic4 action on ethanol responses in mouse brain PFC, where we observed altered LORR after Clic4 over-expression, we performed a genetic correlation analysis using the GeneNetwork web resource (www.genenetwork.org) to identify genes with expression tightly coupled with basal Clic4 expression in PFC across the BXD genetic panel of mice. Clic4 expression was strongly correlated with a large set of genes in PFC (Supplemental Table S1). This gene set was strikingly over-represented (p< 10−15) for a network of genes involved in RNA processing as determined via Ingenuity Pathway Analysis (Supplementary Figure S7 and Supplemental Table S2). This result raises the possibility that Clic4 might influence ethanol sensitivity in mice by functioning within a network of genes that impinge on RNA processing and trafficking.
