A) In Mdr2−/− mice, Aanat expression was reduced in pineal gland, but was enhanced in total liver and cholangiocytes. Aanat expression was increased in pineal gland of Mdr2−/− mice exposed to dark, but was decreased in pineal gland of Mdr2−/− mice treated with melatonin. Data are means ± sem of 6 evaluations from 6 different animals. *P < 0.05 vs. WT mice. #P < 0.05 vs. Mdr2−/− mice. B, C) Aanat expression was enhanced in total liver (B) and cholangiocytes (C) from Mdr2−/− mice, as well as from Mdr2−/− mice treated with melatonin, but was reduced in total liver and cholangiocytes from Mdr2−/− mice exposed to the dark. PCR data are means ± sem of 4 evaluations in cholangiocytes from 3 cumulative preparations of cholangiocytes from 4 mice (n = 12 mice). D) Melatonin serum levels were higher in Mdr2−/− mice than in normal WT mice, as well as in Mdr2−/− mice exposed to dark or treated with melatonin compared with WT mice. Data are means ± sem of 6 evaluations from 6 different animals. *P < 0.05 vs. WT mice. #P < 0.05 vs. Mdr2−/− mice. E, F) AANAT expression (E) and serum melatonin levels (F) were enhanced in male humans with late-stage PSC compared with controls. Data are means ± sem of 3 evaluations from 4 healthy control subjects and 4 male patients with PSC. *P < 0.05 vs. control samples.