TABLE 2

Hematologic and morphologic differences in SAGE knockout rats

RatsMdr1a KnockoutBcrp KnockoutMrp2 Knockout
Number of animals/group4 males4 males4 males
Percent change from wild type
Body weight compared with wild type↑18*↑17*↑32*
HematologyPercent change from wild typea, severityb
 Reticulocyte count↓25, MI↓36, SL
 Hemoglobin↓8, EQ
 Neutrophil count↓31, MI↓51, SL
Clinical chemistryPercent change from wild type, severity
 Urea nitrogen↓10, EQ↓16, EQ↓39, SL
 Creatinine↓12, EQ↓ 8, EQ↓37, SL
 Total bilirubincc↑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 weightsdPercent change from wild type, severity
 Kidney↑24*, SL↑30*, SL↑44*, MO
 Liver↑28*,MI↑22*, MI↑53*, MO
Morphologic pathologyNumber of animals, severity
Liver
 Enlarged (gross)1 MO
 Increased hepatocyte size3 MI-SL4 MI-SL
Kidney
 Discoloration, green (gross)4 MI-SL
 Increased glomerular size4 MI3 MI
 Increased hyaline droplets, PCT4 SL
 Basophilic tubule2 MI1 MI3 MI-SL
Cerebrum
 Ventricular dilation3 SL
Cerebellum
 Molecular layer aplasia, focal1 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