Cyp2e1-flox Mouse

Cyp2e1, short for Cytochrome P450 2E1, is a cytochrome P450 enzyme. It metabolizes alcohol and a variety of other small-molecule compounds, and is a major source of oxidative stress in the body [3,5]. It is involved in the bioactivation of xenobiotics and in eliminating electrophilic agents, reactive oxygen species, and free-radical products [2]. CYP2E1 also plays a role in drug metabolism, and its induction can lead to increased biotransformation of procarcinogens, thus being associated with the risk of chemically-mediated cancers [4].

In alcoholic liver disease (ALD), studies using knockout (KO) mouse models have provided insights. In ERRγ-LKO mice, alcohol-induced upregulation of hepatic FGF23 and plasma FGF23 levels is lost, and an inverse agonist-mediated inhibition of ERRγ transactivation significantly improves alcoholic liver damage. Moreover, hepatic CYP2E1 induction in response to alcohol is FGF23-dependent, and FGF23-LKO mice display decreased hepatic CYP2E1 expression and improved ALD through reduced hepatocyte apoptosis and oxidative stress, indicating that FGF23 may promote ALD through enhancing CYP2E1-mediated hepatic oxidative stress [1]. Also, Cyp2e1 knockout mice are resistant to alcohol-induced gut leakiness and liver inflammation, suggesting a role of Cyp2e1 in alcohol-induced intestinal hyperpermeability which is related to ALD pathogenesis [3].

In conclusion, Cyp2e1 is crucial in alcohol metabolism, oxidative stress regulation, and is associated with multiple disease conditions such as ALD, chemically-mediated cancers, and non-alcoholic fatty liver disease (NAFLD). The use of KO mouse models has been instrumental in revealing its role in ALD, specifically in the context of hepatic oxidative stress and intestinal permeability, providing potential therapeutic targets for these diseases.