uhrf1 is required for liver regeneration. (A) uhrf1 message was detected by standard PCR in rat primary hepatocytes, stellate cells, and whole liver tissue, in human hepatocyte cell lines (Huh7 and Hep3B), and in the stellate cell line (LX2) compared with GAPDH. (B and C) Mouse (B) and zebrafish (C) livers were collected at the indicated times after PH. The expression levels of uhrf1, ccne, and ccna2 were determined by using Q-PCR with cyclophilin as a reference for mouse and ef1a as a reference for zebrafish. Graphs represent fold change compared with quiescent livers. For zebrafish, n = 2 for each PH time point and n = 5 for quiescent liver samples. (D) The level of uhrf1 and top2a transcripts in quiescent (t = 0; n = 3) and regenerating (t = 36 h; n = 3) livers were determined by Q-PCR with ef1a as a reference. Numbers are expressed as the average fold change at 36 h compared with the t = 0 samples. Error bars indicate SD, and P values are labeled. (E) Seven uhrf1+/+ fish and nine uhrf1+/− fish were subject to PH. After 5 days of recovery, the livers were dissected and assessed for regrowth. Representative animals are shown. One hundred percent (7/7) of the uhrf1+/+ animals had substantial regeneration, whereas only 22% (2/7) of the uhrf1+/− animals had any regrowth 5 days after PH.