The Oatp1a/1b Cluster Knockout Mouse was developed in the laboratory of Alfred Schinkel of the Netherlands Cancer Institute in 2010. The model was generated by insertion of loxP sites into the Slco1a5 and Slco1b2 genes at both ends of the Slco1a/1b gene cluster in E14 embryonic stem cells derived from 129P2/OlaHsd mice, followed by Cre-mediated deletion and injecting the targeted cells into C57BL/6J blastocysts. Resultant chimeras were backcrossed to FVB/N mice. Expression of human OATP1B1 and 1B3 in the liver of transgenic mice was achieved by constructing an ApoE promoter-HCR1-driven expression cassette containing either human SLCO1B1 or SLCO1B3 cDNA followed by pronuclear injection into fertilized oocytes of FVB mice. Two-cell stage embryos were implanted into oviducts of pseudopregnant F1 fosters and carried to term. Founders with stable hepatic expression of either human OATP1B1 or OATB1B3 were selected for further crosses with Oatp1a/1b Cluster Knockout Mouse described above. Taconic received sperate stocks of Humanized OATP1B1 and 1B3 Mice in 2010. Humanized OATP1B1 and 1B3 Mice were derived by embryo transfer and were further crossed by Taconic to generate double Humanized OATP1B1/1B3 Mice. These mice are maintained by incrossing of mice homozygous for the Oatp1a/1b Cluster Knockout, the human OATP1B1 transgene and the human OATP1B3 transgene.
Salphati L, Chu X, Chen L, Prasad B, Dallas S, Evers R, Mamaril-Fishman D, Geier EG, Kehler J, Kunta J, Mezler M, Laplanche L, Pang J, Rode A, Soars MG, Unadkat JD, van Waterschoot RA, Yabut J, Schinkel AH, Scheer N. (2014) Evaluation of organic anion transporting polypeptide 1B1 and 1B3 humanized mice as a translational model to study the pharmacokinetics of statins. Drug Metab. Dispos. 42(8):1301-13.
The single humanized models for OATP1B1 and 1B3 were published as follows: van de Steeg E, van Esch A, Wagenaar E, Kenworthy KE, Schinkel AH (2012). Influence of human OATP1B1, OATP1B3, and OATP1A2 on the pharmacokinetics of methotrexate and paclitaxel in humanized transgenic mice. Clin Cancer Res. 2012 Dec 14.