title: Characterization of novel cytochrome P450 2E1 knockout rat model generated by CRISPR/Cas9.
abstract: A bacterial CRISPR-associated protein-9 nuclease (CRISPR/Cas9) from Streptococcus pyogenes has generated considerable excitement as a new tool to edit the targeted genome. Cytochrome P450 (CYP) 2E1 not only plays an important role in the xenobiotic metabolism and chemical toxicity, but also is involved in many kinds of diseases, such as alcoholic liver diseases and diabetes. Despite its importance, few animal models are used to predict CYP2E1 properties in physiology, pathology, as well as carcinogen activation. To establish a novel model for investigating the functions of CYP2E1 in vivo, this study has successfully generated the Cyp2e1 knockout (KO) rat model without detectable off-target effects using CRISPR/Cas9 system. The Cyp2e1 KO rats were viable and fertile and did not display any obvious physiological abnormities. The absent expression of CYP2E1 in KO rats also resulted in inactive behaviors in the metabolism of CYP2E1 substrates. The Cyp2e1 KO rats as a novel and available rodent animal model provide a powerful tool for the study of CYP2E1 in the chemical metabolism, toxicity, carcinogenicity, and its core factor in drug-drug interactions.
authors.affiliation: Shanghai Key Laboratory of Regulatory Biology, Institute of Biomedical Sciences and School of Life Sciences, East China Normal University, Shanghai, China. Electronic address: xwang@bio.ecnu.edu.cn.
authors.forename: Xin
authors.initials: X
authors.lastname: Wang
authors.affiliation: Shanghai Key Laboratory of Regulatory Biology, Institute of Biomedical Sciences and School of Life Sciences, East China Normal University, Shanghai, China.
authors.forename: Yu
authors.initials: Y
authors.lastname: Tang
authors.affiliation: Shanghai Key Laboratory of Regulatory Biology, Institute of Biomedical Sciences and School of Life Sciences, East China Normal University, Shanghai, China.
authors.forename: Jian
authors.initials: J
authors.lastname: Lu
authors.affiliation: Shanghai Key Laboratory of Regulatory Biology, Institute of Biomedical Sciences and School of Life Sciences, East China Normal University, Shanghai, China.
authors.forename: Yanjiao
authors.initials: Y
authors.lastname: Shao
authors.affiliation: Shanghai Key Laboratory of Regulatory Biology, Institute of Biomedical Sciences and School of Life Sciences, East China Normal University, Shanghai, China.
authors.forename: Xuan
authors.initials: X
authors.lastname: Qin
authors.affiliation: Shanghai Key Laboratory of Regulatory Biology, Institute of Biomedical Sciences and School of Life Sciences, East China Normal University, Shanghai, China.
authors.forename: Yongmei
authors.initials: Y
authors.lastname: Li
authors.affiliation: Shanghai Key Laboratory of Regulatory Biology, Institute of Biomedical Sciences and School of Life Sciences, East China Normal University, Shanghai, China.
authors.forename: Liren
authors.initials: L
authors.lastname: Wang
authors.affiliation: Shanghai Key Laboratory of Regulatory Biology, Institute of Biomedical Sciences and School of Life Sciences, East China Normal University, Shanghai, China. Electronic address: dlli@bio.ecnu.edu.cn.
authors.forename: Dali
authors.initials: D
authors.lastname: Li
authors.affiliation: Shanghai Key Laboratory of Regulatory Biology, Institute of Biomedical Sciences and School of Life Sciences, East China Normal University, Shanghai, China; Center for Cancer and Stem Cell Biology, Institute of Biosciences and Technology, Texas A&M University Health Science Center, Houston, TX, USA. Electronic address: myliu@bio.ecnu.edu.cn.
authors.forename: Mingyao
authors.initials: M
authors.lastname: Liu
mesh_terms: D000818:Animals; D001483:Base Sequence; D064113:CRISPR-Cas Systems / Q000502:physiology*; D019392:Cytochrome P-450 CYP2E1 / Q000096:biosynthesis / Q000172:deficiency* / Q000235:genetics*; D005260:Female; D055785:Gene Knockdown Techniques / Q000379:methods*; D008297:Male; D023421:Models, Animal; D008969:Molecular Sequence Data; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D019392:Cytochrome P-450 CYP2E1
keywords: 3-Acetamidophenol (PubChem CID: 12124); 6-Hydroxychlorzoxazone (PubChem CID: 2734); CRISPR/Cas9; CYP2E1; Chlorzoxazone (PubChem CID: 2733); Drug metabolism; Knockout; Rat