administration is needed. Morgan and collaborators reported that in a transgenic mouse overexpressing CYP2E1, ethanol administration produced liver injury [18,19}. We recently reported that CYP2E1 plays a role in experimental fatty liver in an oral, Lieber-DeCarli ethanol feeding model [20]. Fatty liver was observed in wild type mice but not in CYP2E1 knockout mice fed ethanol chronically. The goal of the current report was to extend this previous study to humanized CYP2E1 knockin mice. Because of concerns of extrapolating results with mouse enzymes to human enzymes and to overcome species differences in P450 expression, and specificity between rodents and humans, transgenic humanized mouse models expressing major P450 enzymes were developed by Gonzalez and colleagues [21]. The human P450 transgene was introduced onto the corresponding null mouse background [22] to create a humanized P450 mouse in the absence of the corresponding mouse P450 [23]. Therefore, functional activities and differences between human and mouse CYPs can be directly compared with this model. In the humanized CYP2E1 knockin mouse [23], some differences were observed compared to the wild type mice expressing mouse CYP2E1 such as rates of p-nitrophenol (but not chlorzoxazone) oxidation and sensitivity to toxicity by acetaminophen. A major goal of the
