Humanized CYP3A4/3A7 Mouse

Model Description

• 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.

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

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.

Animal Diet: NIH #31M Rodent Diet

Licensing Requirements:

Label License: Conditions of Use - Model 8842
This Model is produced and distributed under rights to patents and intellectual property owned by Taconic or licensed from various institutions. Taconic sells this model to purchaser, and grants to each purchaser a right under Taconic's own or sublicensable rights in such licensed patents and intellectual property to use the purchased Model in consideration of purchasers' acknowledgement of and agreement to the Terms and Conditions of Sale and the following terms of use:

• Title to this Model and biological materials derived from it remains with TACONIC FARMS, INC.
• The Model will be used for research purposes only.
• The Model will not be bred except to obtain embryos or fetuses required for research purposes
• The Model and biological materials derived from it will not be distributed to third parties or used for commercial purposes
• Non-profit purchasers may not use this Model and/or biological materials derived from it in sponsored research or contract research studies unless it is purchased at the for-profit price.

Pricing for non-profit users (excluding users at non-profit foundations which are affiliated with a for-profit entity):

8842

Humanized CYP3A4/3A7 Mouse European prices for non-profit users

Pricing for for-profit users (including users at non-profit foundations which are affiliated with a for-profit entity):

8842

Humanized CYP3A4/3A7 Mouse European prices for for-profit users

Related Reports

View the production locations(s) and the accompanying current IHMS^TM Health Report and Taconic Health Standard for this model

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