Humanized CYP3A4/3A7 Mouse

Targeted Replacement

Humanized CYP3A4/3A7 Targeted Replacement Mouse Model
EZcohort™ Models
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  • Model #
  • Genotype
  • Nomenclature
  • 8842-F
    hu/hu
    C57BL/6-Del(5Cyp3a57-Cyp3a59)1Artetm1(CYP3A4-CYP3A7)Arte
  • 8842-M
    hu/hu
    C57BL/6-Del(5Cyp3a57-Cyp3a59)1Artetm1(CYP3A4-CYP3A7)Arte
  • This model carries a replacement of seven full-length mouse Cyp3a genes (Cyp3a11, Cyp3a16, Cyp3a25, Cyp3a41, Cyp3a44, Cyp3a57, Cyp3a59) with approximately 125 kb of genomic human DNA comprising CYP3A4 and CYP3A7.
  • CYP3A4 is the most abundant hepatic and intestinal CYP in humans and catalyzes the metabolism of more than 50% of drugs in clinical use.
  • Useful to study human-specific CYP3A4 metabolites and to assess the relevance of CYP3A4 for drug-drug interaction.
  • This model may be used in combination with a Cyp3a knockout model (8841) in order to determine the contribution of CYP3A4-mediated drug metabolism.
Orders by weight: Taconic cannot accept orders by weight for this model. Please note that shipments may contain animals with a larger weight variation.

Genetic Background:

C57BL/6 Background

Origin:

The Humanized CYP3A4/3A7 Mouse model was developed by Taconic in collaboration with CXR Biosciences. The model was created by four consecutive rounds of transfection in C57BL/6NTac-derived ES cells. First, mouse exon 1 and 2 of Cyp3a57 was replaced with a hygromycin cassette containing a loxP, lox5171 and frt site through gene targeting. Second, a neomycin cassette with a loxP and f3 site was inserted into intron 4 of the Cyp3a59 gene through gene targeting. Third, transfection of the ES cells with cre recombinase resulted in the deletion of the Cyp3a57, Cyp3a16, Cyp3a41, Cyp3a44, Cyp3a11, Cyp3a25 and Cyp3a59 genes. Fourth, a modified human bacterial artificial chromosome carrying CYP3A4 and CYP3A7 was inserted by cre-mediated recombination into the loxP and lox5171 sites in the mouse Cyp3a locus. The targeted ES cells were injected into BALB/cJBomTac blastocysts and the resultant chimeras were backcrossed to a Flpe deleter strain on C57BL/6J to eliminate selection markers. Taconic received stock in 2008, and the line was embryo transfer derived. The colony is maintained by mating homozygotes.


Color:

Black

Species:

Mouse

Initial Publication:

Hasegawa M, Kapelyukh Y, Tahara H, Seibler J, Rode A, Krueger S, Lee DN, Wolf CR, Scheer N (2011). Quantitative prediction of human pregnane X receptor and cytochrome P450 3A4 mediated drug-drug interaction in a novel multiple humanized mouse line. Mol Pharmacol 80(3):518-528.



Conditions of Use for EZcohort™ Models
EZcohort™ models are produced and distributed under rights to patents and intellectual property licensed from various institutions. Taconic Biosciences, Inc. (Taconic) sells EZcohort™ models to purchasers, grants to each purchaser a right under Taconic's rights in such licensed patents and intellectual property to use the purchased EZcohort™ models in consideration of purchasers' acknowledgement of and agreement to Taconic's Terms and Conditions for the Sale of Products and the following conditions of use:

  • Title to EZcohort™ models and biological materials derived from them remains with Taconic.
  • EZcohort™ models will be used for research purposes only.
  • EZcohort™ models and biological materials derived from them will not be distributed to third parties or used for commercial purposes.
  • Breeders from deliverables can be used for propagation of EZcohort™ models or to cross to other strains.
  • Continuation of breeding and crossbreeding of EZcohort™ models outside Taconicis permitted for a term of three years post-purchase of the EZcohort™ models and is subject to annual confirmation of these EZcohort™ Conditions of Use.

Continuation of breeding and crossbreeding after the three year term will require renewal of the EZcohort™ Conditions of Use and payment of a fee.