Alcoholic liver disease includes hepatosteatosis (fatty liver), hepatic inflammation, liver fibrosis, cirrhosis, and liver cancer. Fatty liver is a uniform and early response of the liver to alcohol consumption. Alcoholic fatty liver is generally benign, but it is more sensitive to liver injury induced by hepatotoxins such as lipopolysaccharide (Yang et al., 2001). Both cytochromes P450 2A6 (CYP2A6) and CYP2E1 were found to be increased in the liver sections from patients with alcoholic and non-alcoholic fatty liver diseases (Niemela et al., 2000). Using Cyp2e1 knockout (Cyp2e1−/−) mice and Cyp2e1−/− mice reconstituted with human CYP2E1 (humanized CYP2E1 knock-in) mice, we confirmed the important role of CYP2E1 in the development of alcoholic fatty liver disease (Lu et al., 2008, 2010). But it is still unclear whether CYP2A6 also plays an important role in alcoholic fatty liver disease. Recently, we found that CYP2A5, a mouse orthologue of human CYP2A6, was also induced by ethanol in a CYP2E1-dependent manner (Lu et al., 2011). By comparing alcoholic fatty liver disease in Cyp2a5 knockout (Cyp2a5−/−) mice and the corresponding wild-type mice (Cyp2a5+/+), we found that, in
