Model No. | Nomenclature | Genotype |
---|---|---|
9047 | FVB.129P2-Cyp3a13tm1Ahs Del(5Cyp3a57-Cyp3a59)1Ahs Tg(Vil1-CYP3A4)1Ahs | Inquire for genotype |
Model No. | Nomenclature | Genotype |
---|---|---|
9047 | FVB.129P2-Cyp3a13tm1Ahs Del(5Cyp3a57-Cyp3a59)1Ahs Tg(Vil1-CYP3A4)1Ahs | Inquire for genotype |
Nomenclature: FVB.129P2-Cyp3a13tm1Ahs Del(5Cyp3a57-Cyp3a59)1Ahs Tg(Vil1-CYP3A4)1Ahs
Origin
The Gut Humanized CYP3A4 Mouse was developed by Alfred Schinkel at the Netherlands Cancer Institute. The model was generated by targeting of the Cyp3a13 gene in 129P2/OlaHsd-derived E14 ES cells to replace the putative promoter region and exons 1 and 2 with a Pgk-hygromycin cassette. Targeted ES cells were injected into blastocysts. Resultant chimeras were backcrossed to FVB/N for at least seven generations. To generate the cluster deletion, the intronic sequence between exon 2 and 3 of Cyp3a57 was replaced with a neo cassette containing a loxP site, and a hygromycin cassette with a loxP site was inserted downstream of the Cyp3a59 gene in 129P2/OlaHsd-derived E14 ES cells through gene targeting. 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 blastocysts. Resultant chimeras were backcrossed two generations to FVB/N. Mice with the cluster deletion were then backcrossed to the Cyp3a13 targeted mutation line for at least four generations to generate a model with disruption or deletion of all eight full-length mouse Cyp3a genes. The Tg(Vil1-CYP3A4)1Ahs transgene was generated by microinjection into FVB/N zygotes. The Cyp3a knockout line was backcrossed to the Tg(Vil1-CYP3A4)1Ahs line for at least three generations. Taconic received stock in 2008, and the line was embryo transfer derived by mating male and female mice homozygous for both targeted regions and homozygous for the transgene. The line was maintained by mating male and females homozygous for the Cyp3a13 disruption, the cluster deletion and the transgene.
This model is cryopreserved and available for recovery. Models can typically be recovered and delivered to customers within 12 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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Initial Publication:
van Herwaarden AE, Wagenaar E, van der Kruijssen CM, van Waterschoot RA, Smit JW, Song JY, van der Valk MA, van Tellingen O, van der Hoorn JW, Rosing H, Beijnen JH, Schinkel AH. (2007) Knockout of cytochrome P450 3A yields new mouse models for understanding xenobiotic metabolism. J Clin Invest 117(11):3583-92.
Additional Publications:
van Waterschoot RAB, Rooswinkel RW, Sparidans RW, van Herwaarden AE, Beijnen JH, Schinkel AH (2009). Inhibition and stimulation of intestinal and hepatic CYP3A activity: studies in humanized CYP3A4 transgenic mice using triazolam. Drug Metab Disp 37:2305-2313.
van Waterschoot RAB, Rooswinkel RW, Waagenar E, van der Kruijssen CMM, van Herwaarden AE, Schinkel AH (2009). Intestinal cytochrome P450 3A plays an important role in the regulation of detoxifying systems in the liver. FASEB J 23(1): 224-231.
van Waterschoot RAB, ter Heine R, Waagenar E, van der Kruijssen CMM, Rooswinkel RW, Huitema ADR, Beijnen JH, Schinkel AH (2010). Effects of cytochrome P450 3A (CYP3A) and the drug transporters P-glycoprotein (MDR1/ABCB1) and MRP2 (ABCC2) on the pharmacokinetics of lopinavir. Br J Pharmacol 160(5):1224-1233.
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Item | Commercial | Nonprofit |
---|---|---|
Cryopreserved Model | $21,000.00 | $13,000.00 |
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.
Item | Commercial | Nonprofit |
---|---|---|
Cryopreserved Model | €21.000,00 | €13.000,00 |
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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