Global catalase KO (Cat−/−) strain
The Cat KOstrain was developed and characterized by Ho et al. (1). These mice are grossly normal except that their brain mitochondria have a deficiency in mitochondrial respiration (46). Our studies using Cyp2e1 KO mice, acatalasemic (Cs/Cs) mice, and double mutant Cyp2e1−/−/Cs/Cs mice demonstrated these enzymes play a significant role in ethanol sensitivity in the brain (2, 3). Using shRNA-mediated silencing of Cat in the brain, Israel et al. showed ACA to be the active component influencing ethanol preference (4). We recently reported that Cat KO mice develop an obese and pre-diabetic phenotype as they age (5), suggesting that CAT contributes to overall metabolic regulation. Cat KO mice are a valuable model for examining determinants of ethanol drinking preference and alcohol-induced pathophysiology, including obesity.
- Ho YS, Xiong Y, Ma W, Spector A, Ho DS. (2004). Mice lacking catalase develop normally but show differential sensitivity to oxidant tissue injury. J Biol Chem 279: 32804-12.
- Zimatkin SM, Pronko SP, Vasiliou V, Gonzalez FJ, Deitrich RA. (2006). Enzymatic mechanisms of ethanol oxidation in the brain. Alcohol Clin Exp Res 30: 1500-5.
- Vasiliou V, Ziegler TL, Bludeau P, Petersen DR, Gonzalez FJ, Deitrich RA. (2006). CYP2E1 and catalase influence ethanol sensitivity in the central nervous system. Pharmacogenet Genomics 16: 51-8.
- Quintanilla ME, Tampier L, Karahanian E, Rivera-Meza M, Herrera-Marschitz M, Israel Y. (2012). Reward and relapse: complete gene-induced dissociation in an animal model of alcohol dependence. Alcohol Clin Exp Res 36: 517-22.
- Heit C, Marshall S, Singh S, Yu X, Charkoftaki G, Zhao H, Orlicky DJ, Fritz KS, Thompson DC, Vasiliou V. (2017). Catalase deletion promotes prediabetic phenotype in mice. Free Radic Biol Med 103: 48-56.