{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,5,12]],"date-time":"2025-05-12T06:40:10Z","timestamp":1747032010117,"version":"3.40.5"},"reference-count":35,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2025,2,6]],"date-time":"2025-02-06T00:00:00Z","timestamp":1738800000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["31970508"],"award-info":[{"award-number":["31970508"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Anim Models and Exp Med"],"published-print":{"date-parts":[[2025,4]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Liver diseases are a major contributor to both morbidity and mortality. Conditional knockout animals are always produced through crossing floxed animals with a tissue\u2010specific Cre animal. The use of floxed rat resource has rapidly increased, but the liver\u2010specific Cre rat lines for studying liver diseases and interested genes are limited, especially in a spatially and temporally restricted manner.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>RNA sequencing and real\u2010time polymerase chain reaction (PCR) were used to screen and confirm the presence of liver\u2010specific genes. <jats:italic>Apoa4<\/jats:italic>\u2010Cre rats and <jats:italic>Cyp2c11<\/jats:italic><jats:italic>\u2010Cre<\/jats:italic> rats were produced by CRISPR\/Cas9 knockin. Rosa26\u2010imCherry rats were employed to hybridize with the Cre rats to obtain the <jats:italic>Apoa4<\/jats:italic><jats:italic>\u2010Cre<\/jats:italic>\/Rosa26\u2010imCherry and <jats:italic>Cyp2c11<\/jats:italic><jats:italic>\u2010Cre<\/jats:italic>\/Rosa26\u2010imCherry rats. The temporal and spatial patterns of Cre expression were determined by the observation of red fluorescence on tissue sections. Hematoxylin\u2013eosin stain was used to evaluate the liver histopathologic changes. The blood biochemical analysis of several liver enzymes and liver lipid profile was performed to evaluate the liver function of Cre rats.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p><jats:italic>Apoa4<\/jats:italic> and <jats:italic>Cyp2c11<\/jats:italic> were identified as two liver\u2010specific genes. <jats:italic>Apoa4<\/jats:italic><jats:italic>\u2010Cre<\/jats:italic> and <jats:italic>Cyp2c11<\/jats:italic><jats:italic>\u2010Cre<\/jats:italic> rats were produced and hybridized with Rosa26\u2010imCherry rats. The red fluorescence indicated that the Cre recombinases were specially expressed in the juvenile and adult liver and not in other organs of two hybridized rats. All the blood biochemical parameters except low\u2010density lipoprotein (LDL) did not change significantly in the Cre rats. No histological alterations were detected in the livers of the Cre rats.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Liver\u2010specific <jats:italic>Apoa4<\/jats:italic><jats:italic>\u2010Cre<\/jats:italic> and <jats:italic>Cyp2c11<\/jats:italic><jats:italic>\u2010Cre<\/jats:italic> rats have been established successfully and could be used to study gene knockout, specifically in juvenile and adult liver.<\/jats:p><\/jats:sec>","DOI":"10.1002\/ame2.12504","type":"journal-article","created":{"date-parts":[[2025,2,7]],"date-time":"2025-02-07T06:25:11Z","timestamp":1738909511000},"page":"718-727","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Establishment and characterization of liver\u2010specific <i>Apoa4<\/i><i>\u2010<\/i><i>C<\/i><i>re<\/i> and <i>Cyp2c11<\/i><i>\u2010Cre<\/i> rat models in juvenile and adult 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Medical Sciences  Beijing China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jirong","family":"Pan","sequence":"additional","affiliation":[{"name":"Key Laboratory of Human Disease Comparative Medicine, National Health Commission of China (NHC), Institute of Laboratory Animal Science, Peking Union Medicine College Chinese Academy of Medical Sciences  Beijing China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wei","family":"Chen","sequence":"additional","affiliation":[{"name":"Key Laboratory of Human Disease Comparative Medicine, National Health Commission of China (NHC), Institute of Laboratory Animal Science, Peking Union Medicine College Chinese Academy of Medical Sciences  Beijing China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3919-3247","authenticated-orcid":false,"given":"Li","family":"Zhang","sequence":"additional","affiliation":[{"name":"Beijing Engineering Research Center for 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