Phenotypes Associated with This Genotype

Genotype
MGI:3775621

• Allelic Composition: Cyp3a13^tm1Nki/Cyp3a13^tm1Nki; Del(5Cyp3a57-Cyp3a59)2Nki/Del(5Cyp3a57-Cyp3a59)2Nki
• Genetic Background: involves: 129P2/OlaHsd * FVB/N

• ♀: phenotype observed in females
• ♂: phenotype observed in males
• N: normal phenotype

mortality/aging

increased susceptibility to xenobiotic induced morbidity/mortality ( J:127366 )

• administration of 10 mg/kg docetaxel results in death by euthanasia at day 6 and 7 whereas wild-type mice recover to normal weight without lethality by day 25

homeostasis/metabolism

increased susceptibility to xenobiotic induced morbidity/mortality ( J:127366 )

• administration of 10 mg/kg docetaxel results in death by euthanasia at day 6 and 7 whereas wild-type mice recover to normal weight without lethality by day 25

increased physiological sensitivity to xenobiotic ( J:127366 )

• administration of 10 mg/kg docetaxel results in greater weight loss than in wild-type mice and death by euthanasia at day 6 and 7 whereas wild-type mice recover to normal weight without lethality by day 25

abnormal xenobiotic pharmacokinetics ( J:127366 )

• docetaxel M-2 metabolites are not detected in microsomes unlike in wild-type microsomes treated with docetaxel

• the area under the plasma docetaxel concentration versus time curve is 6.8-fold higher than in wild-type mice

• the oral bioavailability of docetaxel is 52% compared to 8.1% in wild-type mice

• docetaxel levels are 7-fold higher in the liver and 5-fold higher in the small intestine compared to in wild-type mice

• clearance of docetaxel is reduced compared to in wild-type mice

• metabolite formation is reduced 24-fold compared to in wild-type mice