Figure 7.

Liver proliferation is inhibited in livers of Gank LKO mice after CCl₄-mediated injury. (A) Examination of liver proliferation by measuring DNA replication (BrdU uptake). Livers were stained with antibodies to BrdU. Arrows show rare BrdU-positive hepatocytes in Gank LKO mice at 48 hours after CCl₄ injections. (B) Calculations of BrdU-positive hepatocytes in livers of LoxP and Gank LKO mice after CCl₄ injections using 2 mice per genotype and per time point and analyzing 3 fields per mouse. P values were as follows: 0 hours (P > .99), 48 hours (P < .001), 72 hours (P > .27), and 96 hours (P > .28). (C) Expression of Gank and cyclin D1 after CCl₄ injury in LoxP and Gank LKO mice using 2 biological replicates. Western blot was performed with nuclear extracts from livers of LoxP and Gank LKO mice. The membrane was reprobed with antibodies to β-actin. Dark and light exposures are shown for Gank. (D) Calculation of levels of Gank and cyclin D1 as ratios to β-actin. Note that low levels of Gank are detected in Gank LKO mice at 24 and 48 hours after CCl₄ injections, perhaps because of proliferation of nonparenchymal cells in which Cre is not expressed. P values for Gankyrin were as follows: 0 hours (P < .0001), 24 hours (P < .0001), and 48 hours (P < .001). P values for cyclin D1 were as follows: 0 hours (P < .25), 24 hours (P > .99), and 48 hours (P < .0009). Two way analysis of variance. ∗P < .05, ∗∗∗P < .001, ∗∗∗∗P < .0001 LoxP vs Gank LKO.