Fig. 4.

Simultaneous ablation of Cdk2 and CcnE1 in hepatocytes restrains liver regeneration after PH. Cdk2^f/f (WT) and Cdk2^ΔhepaCcnE1^−/− mice were subjected to PH and analyzed at 0-336 hours after surgery. (A) Immunofluorescence staining for nuclear BrdU incorporation (green) on liver cryosections 48 hours after PH representing the peak of S-phase. Total nuclei are counter-stained with 4′, 6-diamidino-2-phenylindole (blue). (B) Quantification of BrdU-positive hepatocytes 0-96 hours after PH. (C) Liver-weight/body-weight index (%) was determined for up to 2 weeks (336 hours) after PH. **P < 0.01. (D) Protein expression profiles of phospho-Rb, CcnE1, CcnA2, CcnB1, and PCNA in WT and Cdk2^ΔhepaCcnE1^−/− mice after PH. (E) Whole-liver cell extracts were collected from WT and Cdk2^ΔhepaCcnE1^−/− mice at indicated time points after PH. Native cyclin/Cdk kinase complexes were immunoprecipitated (IP) with antibodies, as indicated, and subjected to in vitro kinase assays using either recombinant Rb or histone H1 as substrate.