- This model carries a deletion of seven full-length mouse Cyp3a genes.
- Contains a cre-mediated deletion of the following genes in the Cyp3a cluster: Cyp3a11, Cyp3a16, Cyp3a25, Cyp3a41, Cyp3a44, Cyp3a57, Cyp3a59.
- In humans, CYP3A enzymes metabolize most drugs.
- Useful in dissecting the contribution of the Cyp3a family to total bioavailability of a drug.
- This model may be used in combination with another model which expresses human CYP3A4 under control of the human CYP3A4 promoter (8842) in order to determine the contribution of CYP3A4-mediated drug metabolism.
Genetic Background:
C57BL/6NTac Background Origin:
The Cyp3a (7-gene) Knockout Mouse was developed by Taconic in collaboration with CXR Biosciences. The model was created by first replacing mouse exon 1 and 2 of Cyp3a57 with a hygromycin cassette containing a loxP site and subsequently inserting a neomycin cassette with a loxP site into intron 4 of the Cyp3a59 gene through gene targeting in C57BL/6NTac-derived ES cells. Transfection of the ES cells with cre recombinase resulted in the deletion of Cyp3a57, Cyp3a16, Cyp3a41, Cyp3a44, Cyp3a11, Cyp3a25 and Cyp3a59. The targeted ES cells were injected into BALB/cJBomTac blastocysts. Resultant chimeras were backcrossed to C57BL/6NTac wild type mice. Taconic received stock in 2008, and the line was embryo transfer derived. The colony was maintained by mating homozygotes. Color:
Black Species:
Mouse Initial Publication:
Scheer N, Ross J, Kapelyukh Y, Rode A, Wolf CR. (2010). In vivo responses of the human and murine pregnane X receptor to dexamethasone in mice.
Drug Metab Disp 38(7) 1046-1053.
Additional 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.
