Pathologic alterations after vivo-morpholino treatment. A and B: Pathologic changes were evaluated in all livers by hematoxylin and eosin (H&E) staining (A) and in serum for alkaline phosphatase (ALP) and γ-glutamyl transferase (γ-GT) levels (B). A: H&E staining reveals no changes between wild-type (WT) groups treated with mismatch or histamine-2 receptor (H2HR) vivo-morpholino, whereas Mdr2−/− (ATP binding cassette subfamily B member 4 null) mice treated with H2HR mismatch display areas of lobular damage, inflammation, and necrosis (white arrows). There is no hepatic damage in multidrug-resistance transporter 2/ABC transporter B family member 2 knockout Mdr2−/− mice treated with H2HR vivo-morpholino. B: Serum levels of ALP (top panel) and γ-GT (bottom panel) remain unchanged in WT groups; however, both markers are increased in serum from Mdr2−/− mice treated with H2HR mismatch. ALP and γ-GT serum levels decrease in Mdr2−/− mice treated with H2HR vivo-morpholino. Data are expressed as means ± SEM. n = 12 experiments for IDEXX. ∗P < 0.05 versus WT mismatch; †P < 0.05 versus Mdr2−/− mice + H2HR vivo-morpholino. Original magnification, ×20 (A).