(A) There was enhanced p16 biliary immunoreactivity in Mdr2−/− compared to normal WT mice, which was decreased in Mdr2−/− mice treated with p16 mismatch Vivo-Morpholino compared to Mdr2−/− mice treated with mismatch Morpholino. Original magnification: 20×. (B) By SA-β-galactosidase (SA-β-GAL) staining in liver sections, there was enhanced biliary senescence in Mdr2−/− compared to WT mice that decreased in Mdr2−/− mice treated with p16 Vivo-Morpholino compared to mismatch-treated Mdr2−/− mice. Original magnification: 10×. (A, B) No changes in p16 immunoreactivity and biliary senescence immunoreactivity were observed between WT mice treated with p16 Vivo-Morpholino and mismatch control. (C) By real-time polymerase chain reaction (PCR), the mRNA expression of p15, p18, p21, p27, p53, and Glb1 increased in cholangiocytes from Mdr2−/− compared to WT mice, but decreased in Mdr2−/− mice treated with p16 Vivo-Morpholino compared to Mdr2−/− mice. Data are mean ± standard error of the mean (SEM) of three evaluations performed in a cumulative preparation of cholangiocytes from four mice *p < 0.05 versus WT mice. #p < 0.05 versus Mdr2−/− mice.