| Model No. | Nomenclature | Genotype |
|---|---|---|
| 9049 | FVB.129P2-Cyp3a13tm1Ahs Del(5Cyp3a57-Cyp3a59)1Ahs Tg(Vil1-CYP3A4)1Ahs Tg(APOE-CYP3A4)A1Ahs |
Humanized Liver & Gut CYP3A4 Mouse
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Overview
Nomenclature: FVB.129P2-Cyp3a13tm1Ahs Del(5Cyp3a57-Cyp3a59)1Ahs Tg(Vil1-CYP3A4)1Ahs Tg(APOE-CYP3A4)A1Ahs
- This model carries disruptions or deletions of all eight full-length mouse Cyp3a genes identified as well as two transgenes encoding human CYP3A4 under the control of either a liver-specific promoter (human APOE) and a gut-specific promoter (mouse villin).
- Contains two targeted regions, a single gene knockout of the Cyp3a13 gene, and a cre-mediated deletion of the following gene cluster: Cyp3a11, Cyp3a16, Cyp3a25, Cyp3a41, Cyp3a44, Cyp3a57, Cyp3a58-ps, Cyp3a59.
- In humans, CYP3A enzymes metabolize most drugs.
- Model 9011 serves as the knockout control.
- May be used as a bioreactor to generate human-specific metabolites and study their in vivo effects.
- May be used with Model 9047, which has gut-specific expression of human CYP3A4, and Model 9048, which has liver-specific expression of human CYP3A4.
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
Guides & Publications
Initial Publication:
- van Herwaarden AE, Smit JW, Sparidans RW, Wagenaar E, van der Kruijssen CM, Schellens JH, Beijnen JH, Schinkel AH. (2005) Midazolam and cyclosporin a metabolism in transgenic mice with liver-specific expression of human CYP3A4. Drug Metab Dispos 33(7):892-5.
- 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.
Applications & Therapeutic Areas
- ADMET
- Metabolic Disease
- Microbiome
- Safety Assessment
Transit, Housing & Welfare
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Diet
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- Licensing
- Pricing - USD
- Pricing - EUR
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Humanized Liver & Gut CYP3A4 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.
This model is sold under terms which grant perpetual use rights.
Pricing - USD
9049
| Item | Commercial | Nonprofit |
|---|---|---|
| Cryopreserved Model | $34,650.00 | $23,100.00 |
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
9049
| Item | Commercial | Nonprofit |
|---|---|---|
| Cryopreserved Model | €26.250,00 | €22.050,00 |
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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