首页|Characterization of organic anion transporting polypeptide 1b2 knockout rats generated by CRISPR/Cas9: a novel model for drug transport and hyperbilirubinemia disease

Characterization of organic anion transporting polypeptide 1b2 knockout rats generated by CRISPR/Cas9: a novel model for drug transport and hyperbilirubinemia disease

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Organic anion transporting polypeptide 1B1 and 1B3 (OATP1B1/3) as important uptake transporters play a fundamental role in the transportation of exogenous drugs and endogenous substances into cells.Rat OATP1B2,encoded by the Slcolb2 gene,is homologous to human OATP1B1/3.Although OATP1B 1/3 is very important,few animal models can be used to study its properties.In this report,we successfully constructed the Slco1b2 knockout (KO) rat model via using the CRISPR/Cas9 technology for the first time.The novel rat model showed the absence of OATP1B2 protein expression,with no offtarget effects as well as compensatory regulation of other transporters.Further pharmacokinetic study of pitavastatin,a typical substrate of OATP1B2,confirmed the OATP1B2 function was absent.Since bilirubin and bile acids are the substrates of OATP1B2,the contents of total bilirubin,direct bilirubin,indirect bilirubin,and total bile acids in serum are significantly higher in Slco1b2 KO rats than the data of wild-type rats.These results are consistent with the symptoms caused by the absence of OATP1B1/3 in Rotor syndrome.Therefore,this rat model is not only a powerful tool for the study of OATP 1B2-mediated drug transportation,but also a good disease model to study hyperbilirubinemia-related diseases.

OATP1B1/3OATP1B2CRISPR/Cas9TransporterRat model

Xinrun Ma、Xuyang Shang、Xuan Qin、Jian Lu、Mingyao Liu、Xin Wang

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Shanghai Key Laboratory of Regulatory Biology, Institute of Biomedical Sciences and School of Life Sciences, East China Normal University, Shanghai 200241, China

This work was supported in whole or part by grants from the National Natural Science Foundation of China (No81773808),the SciencThis work was supported in whole or part by grants from the National Natural Science Foundation of China (No81773808),the SciencThis work was supported in whole or part by grants from the National Natural Science Foundation of China (No81773808),the Scienc

Nos171409010001714090100118430760400This work was also supported f

2020

药学学报(英文版)

药学学报(英文版)

CSTPCDCSCDSCI
ISSN：
年,卷(期)：2020.10(5)
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