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Transgenic Analysis of Human Drug–Metabolizing Enzymes: Preclinical Drug Development and Toxicology
Table 3.
Cytochrome P450 Gene Deletions
| P450 | Constitutive Phenotype | Genetic Background | Comments | Citation |
|---|---|---|---|---|
| CYP1A1 | None | 129xC57BL/6 | Protection against BaP toxicity | (4) |
| CYP1A2 | Respiratory distress | 129xC57BL/6 | Disruption of exon 2 Incomplete penetrance | (6, 10) |
| None | 129xCF-1 | Disruption of exon 2, removal of exons 3–5 | ||
| Deficient zoxazolamine metabolism | ||||
| CYP1B1 | None | 129xC57BL/6 | Protection against DMBA-induced bone marrow cytotoxicity and ovarian cancer | (11) |
| CYP2E1 | None | 129xC57BL/6 | Resistant to acetaminophen, chloroform and carbon tetrachloride hepatotoxicity | (12) |
| CPR (liver-specific)[HRN™] | Altered hepatic lipid homeostasis | 129xC57BL/6 C57BL/6 | No hepatic P450 function, altered drug pharmacokinetics, reduced acetaminophen toxicity | (23, 26) |
| CYP7A1 | Lethal in postnatal period (<18d) | 129xC57BL/6 | Rescued by dietary supplementation Alternative bile acid biosynthetic pathway induced | (14, 15) |
| CYP19 | Females infertile Precocious follicular depletion | 129xC57BL/6 | Disruption of exon 9 Partial rescue with estradiol treatment | (17) |
| Females infertile Corpora lutea absent | 129xC57BL/6 | Disruption of exon 9 Enlargement of prostate gland Increased adiposity | (16) | |
| CYP26A1 | Embryonic lethal, mid-late gestation | 129xC57BL/6 | Deletion of exons 2–6 Spina bifida, sirenomelia, caudal truncation | (18) |
| Lethal in perinatal period (<24h) | 129xC57BL/6 | Deletion of entire gene Caudal truncation, vertebra transformation, hindbrain mispatterning | (19) |
