Analysis Tools
normal phenotype
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• hematological, plasma clinical chemistry and pathological examination reveal no abnormalities
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Allele Symbol Allele Name Allele ID |
Cyp3a13tm1Nki targeted mutation 1, The Netherlands Cancer Institute MGI:3764486 |
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| Summary |
4 genotypes
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• hematological, plasma clinical chemistry and pathological examination reveal no abnormalities
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• 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
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• 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
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• 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
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• 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
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• docetaxel M-2 metabolites are not detected in hepatic microsomes unlike in wild-type microsomes treated with docetaxel
• however, M-2 metabolites are detected in intestinal microsomes
• docetaxel accumulation in the small intestines is decreased 4-fold compared to in Del(15Cyp3a57-Cyp3a59)1Ahs Cyp3a13tm1Ahs homozygotes following intravenous injection of docetaxel
• however, upon oral administration of docetaxel plasma levels are reduced 16.6 fold compared to in Del(15Cyp3a57-Cyp3a59)1Ahs Cyp3a13tm1Ahs homozygotes
• oral bioavailability is decreased to 1.8% compared to 8.1% in wild-type mice
• clearance of docetaxel is reduced compared to in wild-type mice
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• docetaxel M-2 metabolites are not detected in intestinal microsomes unlike in wild-type microsomes treated with docetaxel
• plasma docetaxel are higher than in wild-type mice following intravenous administration
• oral administration of docetaxel results in a 2.2-fold reduction of plasma levels compared to in Del(15Cyp3a57-Cyp3a59)1Ahs Cyp3a13tm1Ahs homozygotes
• however, M-2 metabolites are detected in hepatic microsomes
• docetaxel accumulation in the liver is decreased 19-fold compared to in Del(15Cyp3a57-Cyp3a59)1Ahs Cyp3a13tm1Ahs homozygotes
• however, plasma docetaxel levels following intravenous injection are decreased 5.5-fold compared to in Del(15Cyp3a57-Cyp3a59)1Ahs Cyp3a13tm1Ahs homozygotes to near normal levels and mice exhibit near normal clearance of docetaxel
• oral bioavailability is increased to 21% compared to 8.1% in wild-type mice
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Mouse Genome Database (MGD), Gene Expression Database (GXD), Mouse Models of Human Cancer database (MMHCdb) (formerly Mouse Tumor Biology (MTB)), Gene Ontology (GO) |
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last database update 04/09/2024 MGI 6.23 |
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