Fig. 4. Intrahepatic bile duct status in mutant mice. (A,B) Immunostaining for cytokeratin (CK) on control (CO) and mutant (M) liver sections, isolated two months after birth. (A) Control livers contain a large number of well differentiated bile ducts with a layer of CK-positive cells surrounding a lumen (arrowheads). (B) Mutant livers present a very disorganized biliary system. Most portal tracts do not contain any bile duct or CK-positive cell. Hepatocyte necrosis, inflammation and oval cell proliferation are also seen in mutant livers at this stage. (C,D) Histological analysis of the larger intrahepatic bile ducts on control and mutant animals. Arrows in C indicate two normal bile ducts. The ducts of different size feature a single-layer epithelium with regularly spaced nuclei. By contrast, mutant bile ducts present a disorganized multi-layered epithelium (arrow in D). bd, bile duct; pv, portal vein. Scale bars: 1 mm in A,B; 100 µm in C,D.