{"@context":{"@vocab":"https://cir.nii.ac.jp/schema/1.0/","rdfs":"http://www.w3.org/2000/01/rdf-schema#","dc":"http://purl.org/dc/elements/1.1/","dcterms":"http://purl.org/dc/terms/","foaf":"http://xmlns.com/foaf/0.1/","prism":"http://prismstandard.org/namespaces/basic/2.0/","cinii":"http://ci.nii.ac.jp/ns/1.0/","datacite":"https://schema.datacite.org/meta/kernel-4/","ndl":"http://ndl.go.jp/dcndl/terms/","jpcoar":"https://github.com/JPCOAR/schema/blob/master/2.0/"},"@id":"https://cir.nii.ac.jp/crid/1363670320874435072.json","@type":"Article","productIdentifier":[{"identifier":{"@type":"DOI","@value":"10.1038/srep42922"}},{"identifier":{"@type":"URI","@value":"https://www.nature.com/articles/srep42922"}},{"identifier":{"@type":"URI","@value":"https://www.nature.com/articles/srep42922.pdf"}}],"dc:title":[{"@value":"CRISPR knockout rat cytochrome P450 3A1/2 model for advancing drug metabolism and pharmacokinetics research"}],"description":[{"type":"abstract","notation":[{"@value":"<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>"}]}],"creator":[{"@id":"https://cir.nii.ac.jp/crid/1383670320874435073","@type":"Researcher","foaf:name":[{"@value":"Jian Lu"}]},{"@id":"https://cir.nii.ac.jp/crid/1383670320874435075","@type":"Researcher","foaf:name":[{"@value":"Yanjiao Shao"}]},{"@id":"https://cir.nii.ac.jp/crid/1383670320874435201","@type":"Researcher","foaf:name":[{"@value":"Xuan Qin"}]},{"@id":"https://cir.nii.ac.jp/crid/1383670320874435074","@type":"Researcher","foaf:name":[{"@value":"Daozhi Liu"}]},{"@id":"https://cir.nii.ac.jp/crid/1383670320874435202","@type":"Researcher","foaf:name":[{"@value":"Ang Chen"}]},{"@id":"https://cir.nii.ac.jp/crid/1383670320874435200","@type":"Researcher","foaf:name":[{"@value":"Dali Li"}]},{"@id":"https://cir.nii.ac.jp/crid/1383670320874435072","@type":"Researcher","foaf:name":[{"@value":"Mingyao Liu"}]},{"@id":"https://cir.nii.ac.jp/crid/1383670320874435076","@type":"Researcher","foaf:name":[{"@value":"Xin Wang"}]}],"publication":{"publicationIdentifier":[{"@type":"EISSN","@value":"20452322"}],"prism:publicationName":[{"@value":"Scientific Reports"}],"dc:publisher":[{"@value":"Springer Science and Business Media LLC"}],"prism:publicationDate":"2017-02-20","prism:volume":"7","prism:number":"1","prism:startingPage":"42922"},"reviewed":"false","dc:rights":["https://creativecommons.org/licenses/by/4.0","https://creativecommons.org/licenses/by/4.0"],"url":[{"@id":"https://www.nature.com/articles/srep42922"},{"@id":"https://www.nature.com/articles/srep42922.pdf"}],"createdAt":"2017-02-20","modifiedAt":"2022-12-23","relatedProduct":[{"@id":"https://cir.nii.ac.jp/crid/1360013245405548544","@type":"Article","resourceType":"学術雑誌論文(journal article)","relationType":["isReferencedBy"],"jpcoar:relatedTitle":[{"@value":"Recent Advances in the Production of Genome-Edited Rats"}]},{"@id":"https://cir.nii.ac.jp/crid/1360848658894826624","@type":"Article","resourceType":"学術雑誌論文(journal article)","relationType":["isReferencedBy"],"jpcoar:relatedTitle":[{"@value":"Humanized UGT2 and CYP3A transchromosomic rats for improved prediction of human drug metabolism"}]},{"@id":"https://cir.nii.ac.jp/crid/1361694368239404928","@type":"Article","resourceType":"学術雑誌論文(journal article)","relationType":["isReferencedBy"],"jpcoar:relatedTitle":[{"@value":"Generation of novel genetically modified rats to reveal the molecular mechanisms of vitamin D actions"}]}],"dataSourceIdentifier":[{"@type":"CROSSREF","@value":"10.1038/srep42922"},{"@type":"CROSSREF","@value":"10.3390/ijms23052548_references_DOI_TrIHt9xxLn6p18kKBIBct6gaq9d"},{"@type":"CROSSREF","@value":"10.1073/pnas.1808255116_references_DOI_TrIHt9xxLn6p18kKBIBct6gaq9d"},{"@type":"CROSSREF","@value":"10.1038/s41598-020-62048-1_references_DOI_TrIHt9xxLn6p18kKBIBct6gaq9d"}]}