All genetic manipulations of Clic that we investigated led to altered ethanol-response behavior. The observed phenotypes between or even within a species, however, were not identical. Although we currently do not understand the range of phenotypes observed in animals with altered Clic expression, one possible explanation is that CLIC proteins could be direct targets of ethanol, but different Clic genes might be expressed in different cells (e.g. excitatory versus inhibitory neurons) leading to varying effects on ethanol responses. The C. elegans CLIC protein EXL-1 is expressed in PVD and CAN neurons in addition to neurons that have not been identified, while EXC-4, the other CLIC protein in worms, is expressed in a distinct but somewhat overlapping pattern in the nervous system (Berry et al., 2003, Berry & Hobert, 2006). Additionally, while both EXL-1 and EXC-4 are expressed in the intestine, EXL-1 is expressed in body muscle and coloemocytes whereas EXC-4 is localized to the excretory canal cell, hypodermis, sheath cells, rectal gland and vulval cells (Berry & Hobert, 2006). Although the connections between these various cells or tissues and ethanol
