Humanized OATP1B1/1B3 Mouse

Humanized OATP1B1/1B3 Constitutive Knockout/Random Transgenic Mouse Model
  • Cryopreserved
  • Mouse
  • Not available for direct purchase by CRO
Model No.NomenclatureGenotype
11594FVB.129P2-Del(Slco1b2-Slco1a5)1Ahs Tg(APOE-SLCO1B1)1Ahs Tg(APOE-SLCO1B3)1AhsInquire for genotype
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Overview

Nomenclature: FVB.129P2-Del(Slco1b2-Slco1a5)1Ahs Tg(APOE-SLCO1B1)1Ahs Tg(APOE-SLCO1B3)1Ahs

  • This model carries a deletion of all five established Slco1a and 1b and two predicted Slco1a-like mouse genes as well as random transgenic insertions of human SLCO1B1 (OATP1B1) and SLCO1B3 (OATP1B3) under control of the liver specific ApoE promoter.
  • Contains a cre-mediated deletion of the following established genes in the Slco1a/1b cluster: Slco1a1, Slco1a4, Slco1a5, Slco1a6 and Slco1b2.
  • SLCO1B1 (OATP1B1) and SLCO1B3 (OATP1B3) are important hepatic uptake transporters that can transport a wide variety of drugs, such as many statins.
  • Useful in dissecting the role of human OATP1B1 and OATP1B3 in hepatic liver uptake, drug-drug interaction, drug-induced hyperbilirubinemia and drug toxicity.
Orders by weight: Taconic cannot accept orders by weight for this model. Please note that shipments may contain animals with a larger weight variation.

Origin

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 were maintained by incrossing of mice homozygous for the Oatp1a/1b Cluster Knockout, the human OATP1B1 transgene and the human OATP1B3 transgene.

This model is cryopreserved and available for recovery. Models can typically be recovered and delivered to customers within 14-16 weeks after order receipt. Purchase of this model includes perpetual use rights and a deliverable of four mutant animals at the Murine Pathogen Free™ health standard along with a genotyping protocol. For models which include a recombinase gene or multiple alleles, all alleles will be provided, but individual animals may not contain all mutant alleles.

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Genetics

Species:Mouse
Strain Type:Congenic
Allele Type:Constitutive Knockout;Random Transgenic;Genetically Humanized
Genetic Background:FVB

Guides & Publications

Initial Publication: 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.

Applications & Therapeutic Areas

  • ADMET
  • Metabolic Disease
  • Safety Assessment

Transit, Housing & Welfare

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Humanized OATP1B1/1B3 Mouse

Customers may purchase this model by signing the appropriate Terms of Sale (below) and providing a PO.
This model is sold under terms which grant perpetual use rights.

Pricing - USD

11594

ItemCommercialNonprofit
Cryopreserved Model$40,950.00$29,400.00

Cryopreserved models are invoiced upon shipment of recovered animals. Once orders are placed, the full purchase price will be applied if the order is canceled. For orders greater than 4 animals, please contact Taconic for options.

Fees for Taconic Transit Cages™ and freight are in addition to the price above.

Pricing - EUR

11594

ItemCommercialNonprofit
Cryopreserved Model€36.750,00€26.250,00

Cryopreserved models are invoiced upon shipment of recovered animals. Once orders are placed, the full purchase price will be applied if the order is canceled. For orders greater than 4 animals, please contact Taconic for options.

Fees for Taconic Transit Cages™ and freight are in addition to the price above.

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