Figure 1. Alb-Cre-driven NS deletion causes liver damage associated with bile duct hyperplasia.

(A) (Top) Northern blots show a significant upregulation of NS transcripts in CCl₄-injured livers (8-week-old). The increase of NS peaks on the first day of the injection. (Bottom) the percentage of BrdU-labeled hepatocytes reaches plateau on the second day of the injection. (B) Southern blots (hybridized with 5’-probe or 3’-probe) confirm the genotypes of the NS^flxneo and NS^flx alleles. (C) qRT-PCR assays verify the decrease of NS (top) and the increase of Cre (bottom) in albNS^cko livers compared to age-matched NS^flx/flx livers from 1 to 4 weeks old. (D) At 4 weeks, albNS^cko livers display a nodular appearance. (E1) The H&E histology of 4-week-old albNS^cko livers shows hepatic lobules surrounded by hyperplastic bile ducts. Insets show enlarged images of the rectangles. (E2) These hyperplastic bile ducts express CK-19. Bottom panels show images of NS^flx/flx livers. (E3) From 3 weeks of age, necrotic foci can be seen in the albNS^cko liver parenchyma. The bottom panel shows an enlarged view of the rectangular region in the top panel. (F) The liver-to-body weight ratio of albNS^cko mice increases over that of NS^flx/flx mice from 3 weeks old. Bar and line graphs represent mean ± SEM. *, p < 0.01, **, p < 0.001, ***, p < 0.0001. Scale bars, 100um in (E1, E2, E3 top) and 25um in (E3 bottom).