All six genes selected for validation have important roles in peripheral immune and inflammatory signaling and global deletion of these genes may affect multiple tissues. For example, mice deficient in β2-microglobulin fail to express major histocompatibility complex (MHC) class I products (Rothenberg and Voland, 1996), and Cd14-deficient mice are resistant to LPS (Schütt, 1999). Ctss is a key enzyme controlling MHC class II-mediated antigen presentation by epithelial cells in vivo (Beers et al., 2005), and inflammatory responses are compromised in Il6-deficient mice (Kopf et al., 1994). In addition, we found that deletion of related proinflammatory mediators (the chemokines Ccl1 and Ccl2 or the chemokine receptor Ccr2) reduced alcohol preference and intake and also reduced the motivational effect of ethanol in a conditioned taste aversion paradigm (Blednov et al., 2005). Thus, we now have nine genes with roles in immune and inflammatory processes that regulate alcohol consumption. However, as discussed below, these genes should not be considered as exclusively ‘immune’ or ‘inflammatory’ as their role in normal brain signaling is an area of intense investigation. This raises the possibility that the
