Construction and characterization of a humanized SLCO1B1 rat model with its application in evaluating the uptake of different statins
作者机构：Changning Maternity and Infant Health Hospital and School of Life SciencesShanghai Key Laboratory of Regulatory BiologyEast China Normal UniversityShanghai 200241China
出 版 物：《Acta Pharmaceutica Sinica B》 (药学学报（英文版）)
年 卷 期：2024年第14卷第4期
页 面：1592-1604页
核心收录：
学科分类：1002[医学-临床医学] 100206[医学-皮肤病与性病学] 10[医学]
基 金：This work was supported by grants from the National Natural Science Foundation of China(82274010) the Science and Technology Commission of Shanghai Municipality(18430760400,China) the East China Normal University(ECNU)Medicine and Health Joint Fund(2022JKXYD09004,China) the Jointed PI Program from Shanghai Changning Maternity and Infant Health Hospital ECNU Construction Fund of Innovation and Entrepreneurship Laboratory
主 题：CRISPR/Cas9 Drug transport Drug disposition Geneediting Humanized rat model OATP1B1 SLCO1B1 Statins
摘 要：Organic anion-transporting polypeptides IB1(OATPIB1)plays a crucial role in the transport of ***,there are too few animal models related to OATPIB1,especially humanized animal *** this study,the human SLCOIB1 cDNA was inserted into the second exon of the rat Slcolb2 gene using CRISPR/Cas9 *** characteristics of statins were conducted in wild-type(WT),humanized OATPIB1(hOATPIB1),and OATPIB2 knockout(OATPIB2 KO)rats,*** results showed that human OATPIB1 was successfully expressed in rat liver and exhibited transport ***,the pharmacokinetic results revealed that OATPIB1 exhibited varying uptake levels of pivastatin,rosuvastatin,and fluvastatin,leading to different levels of exposure within the *** results were consistent with those obtained from in vitro experiments using overexpressed cell *** conclusion,we established a novel humanized SLCOIBI transgenic rat model to assess the role of human OATPIB1 in the uptake of different *** different uptake mediated by OATPIB1 may be an important reason for the different efficacy of *** hOATPIB1 rat is a promising model for improving the prediction of human drug transport.
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