Phenotypes associated with this allele

• Allele Symbol: Del(5Cyp3a57-Cyp3a59)2Nki
• Allele Name: deletion, Chr 5, The Netherlands Cancer Institute 2
• Allele ID: MGI:3775604
• Summary: 4 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
hm1	Del(5Cyp3a57-Cyp3a59)2Nki/Del(5Cyp3a57-Cyp3a59)2Nki	involves: 129P2/OlaHsd	MGI:3775620
cx2	Cyp3a13^tm1Nki/Cyp3a13^tm1Nki Del(5Cyp3a57-Cyp3a59)2Nki/Del(5Cyp3a57-Cyp3a59)2Nki	involves: 129P2/OlaHsd * FVB/N	MGI:3775621
cx3	Cyp3a13^tm1Nki/Cyp3a13^tm1Nki Del(5Cyp3a57-Cyp3a59)2Nki/Del(5Cyp3a57-Cyp3a59)2Nki Tg(Vil1-CYP3A4)1Nki/0	involves: 129P2/OlaHsd * FVB/N	MGI:3775625
cx4	Cyp3a13^tm1Nki/Cyp3a13^tm1Nki Del(5Cyp3a57-Cyp3a59)2Nki/Del(5Cyp3a57-Cyp3a59)2Nki Tg(APOE-CYP3A4)A1Nki/0	involves: 129P2/OlaHsd * FVB/N	MGI:3775628

Genotype
MGI:3775620

hm1

• Allelic Composition: Del(5Cyp3a57-Cyp3a59)2Nki/Del(5Cyp3a57-Cyp3a59)2Nki
• Genetic Background: involves: 129P2/OlaHsd

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

normal phenotype

no abnormal phenotype detected ( J:127366 )

• hematological, plasma clinical chemistry and pathological examination reveal no abnormalities

Genotype
MGI:3775621

cx2

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

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

Genotype
MGI:3775625

cx3

• Allelic Composition: Cyp3a13^tm1Nki/Cyp3a13^tm1Nki; Del(5Cyp3a57-Cyp3a59)2Nki/Del(5Cyp3a57-Cyp3a59)2Nki; Tg(Vil1-CYP3A4)1Nki/0
• Genetic Background: involves: 129P2/OlaHsd * FVB/N

homeostasis/metabolism

abnormal xenobiotic pharmacokinetics ( J:127366 )

• 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 Cyp3a13^tm1Ahs 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 Cyp3a13^tm1Ahs 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

Genotype
MGI:3775628

cx4

• Allelic Composition: Cyp3a13^tm1Nki/Cyp3a13^tm1Nki; Del(5Cyp3a57-Cyp3a59)2Nki/Del(5Cyp3a57-Cyp3a59)2Nki; Tg(APOE-CYP3A4)A1Nki/0
• Genetic Background: involves: 129P2/OlaHsd * FVB/N

homeostasis/metabolism

abnormal xenobiotic pharmacokinetics ( J:127366 )

• 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 Cyp3a13^tm1Ahs 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 Cyp3a13^tm1Ahs homozygotes

• however, plasma docetaxel levels following intravenous injection are decreased 5.5-fold compared to in Del(15Cyp3a57-Cyp3a59)1Ahs Cyp3a13^tm1Ahs 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