CRISPR knockout rat cytochrome P450 3A1/2 model for advancing drug metabolism and pharmacokinetics research
書誌事項
- 公開日
- 2017-02-20
- 権利情報
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- https://creativecommons.org/licenses/by/4.0
- https://creativecommons.org/licenses/by/4.0
- DOI
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- 10.1038/srep42922
- 公開者
- Springer Science and Business Media LLC
説明
<jats:title>Abstract</jats:title><jats:p>Cytochrome P450 (CYP) 3A accounts for nearly 30% of the total CYP enzymes in the human liver and participates in the metabolism of over 50% of clinical drugs. Moreover, CYP3A plays an important role in chemical metabolism, toxicity, and carcinogenicity. New animal models are needed to investigate CYP3A functions, especially for drug metabolism. In this report, <jats:italic>Cyp3a1/2</jats:italic> double knockout (KO) rats were generated by CRISPR-Cas9 technology, and then were characterized for viability and physiological status. The <jats:italic>Cyp3a1/2</jats:italic> double KO rats were viable and fertile, and had no obvious physiological abnormities. Compared with the wild-type (WT) rat, <jats:italic>Cyp3a1/2</jats:italic> expression was completely absent in the liver of the KO rat. <jats:italic>In vitro</jats:italic> and <jats:italic>in vivo</jats:italic> metabolic studies of the CYP3A1/2 substrates indicated that CYP3A1/2 was functionally inactive in double KO rats. The <jats:italic>Cyp3a1/2</jats:italic> double KO rat model was successfully generated and characterized. The <jats:italic>Cyp3a1/2</jats:italic> KO rats are a novel rodent animal model that will be a powerful tool for the study of the physiological and pharmacological roles of CYP3A, especially in drug and chemical metabolism <jats:italic>in vivo</jats:italic>.</jats:p>
収録刊行物
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- Scientific Reports
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Scientific Reports 7 (1), 42922-, 2017-02-20
Springer Science and Business Media LLC
