Format

Send to

Choose Destination
Biochem Pharmacol. 2016 Apr 1;105:80-90. doi: 10.1016/j.bcp.2016.03.001. Epub 2016 Mar 3.

Characterization of novel cytochrome P450 2E1 knockout rat model generated by CRISPR/Cas9.

Author information

1
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.
2
Shanghai Key Laboratory of Regulatory Biology, Institute of Biomedical Sciences and School of Life Sciences, East China Normal University, Shanghai, China.
3
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.
4
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.

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.

KEYWORDS:

3-Acetamidophenol (PubChem CID: 12124); 6-Hydroxychlorzoxazone (PubChem CID: 2734); CRISPR/Cas9; CYP2E1; Chlorzoxazone (PubChem CID: 2733); Drug metabolism; Knockout; Rat

PMID:
26947455
DOI:
10.1016/j.bcp.2016.03.001
[Indexed for MEDLINE]

Supplemental Content

Full text links

Icon for Elsevier Science
Loading ...
Support Center