Rats | Mdr1a Knockout | Bcrp Knockout | Mrp2 Knockout |
---|---|---|---|
Number of animals/group | 4 males | 4 males | 4 males |
Percent change from wild type | |||
Body weight compared with wild type | ↑18* | ↑17* | ↑32* |
Hematology | Percent change from wild typea, severityb | ||
Reticulocyte count | — | ↓25, MI | ↓36, SL |
Hemoglobin | ↓8, EQ | — | — |
Neutrophil count | — | ↓31, MI | ↓51, SL |
Clinical chemistry | Percent change from wild type, severity | ||
Urea nitrogen | ↓10, EQ | ↓16, EQ | ↓39, SL |
Creatinine | ↓12, EQ | ↓ 8, EQ | ↓37, SL |
Total bilirubin | —c | –c | ↑3800, MA |
ALP | ↑72, MI | ↑65, MI | — |
ALT | ↓14, EQ | ↓ 21, EQ | ↓ 24, EQ |
AST | ↓29, MI | ↓9, EQ | ↓ 18, EQ |
CK | ↓32, EQ | — | ↓51, EQ |
Glucose | ↑26, EQ | ↑39, MI | ↑50, MI |
Cholesterol | ↓23, MI | ↓32, SL | ↑25, EQ |
Triglyceride | ↑89, SL | ↓32, SL | ↑62, MI |
Relative organ weightsd | Percent change from wild type, severity | ||
Kidney | ↑24*, SL | ↑30*, SL | ↑44*, MO |
Liver | ↑28*,MI | ↑22*, MI | ↑53*, MO |
Morphologic pathology | Number of animals, severity | ||
Liver | |||
Enlarged (gross) | — | — | 1 MO |
Increased hepatocyte size | 3 MI-SL | — | 4 MI-SL |
Kidney | |||
Discoloration, green (gross) | — | — | 4 MI-SL |
Increased glomerular size | — | 4 MI | 3 MI |
Increased hyaline droplets, PCT | — | — | 4 SL |
Basophilic tubule | 2 MI | 1 MI | 3 MI-SL |
Cerebrum | |||
Ventricular dilation | — | 3 SL | — |
Cerebellum | |||
Molecular layer aplasia, focal | 1 P | — | — |
—, not different from wild type or finding not present; ↑, increased; ↓, decreased; ALP, alkaline phosphatase; ALT, alanine aminotransferase; AST, aspartate transaminase; CK, creatine kinase.
↵a Percent change from wild type = [(knockout value – wild type value)/(wild-type value)] × 100%.
↵b Severity grading scale: present, no grade assigned (P), equivocal (EQ), minimal (MI), slight (SL), moderate (MO), marked (MA), severe (SE).
↵c All individual total bilirubin values for this group were below the lower limit of quantification for the assay.
↵d Organ weight relative to body weight.
* P < 0.05