Fig. 6.

VKO mice display a loss of hepatocyte zonation and abnormal overlap of hepatocyte zonal markers. To assess hepatocyte zonation in VKO mice, we assessed the expression of carbamoyl phosphate synthetase 1 (CPS1), a marker of periportal and intermediate zone hepatocytes, and the coexpression of CPS1 and GS. In control mice, CPS1 begins to exhibit zonal restriction at P15 (A), and, by P30, expression of CPS1 is excluded from pericentral hepatocytes (C). At both P15 and P30, control mice do not display overlap in the expression patterns of CPS1 and GS (E and G). In VKO mice, similar to controls, rough zonal restriction of CPS1 expression is observed at P15 (B). However, by P30, there is a loss of zonal pattern of CPS1 expression in VKO mice (D). VKO mice also display the abnormal coexpression of GS and CPS1 in both pericentral hepatocytes and in intermediate zone hepatocytes that abnormally express GS (arrowheads). This coexpression occurs in rare hepatocytes at P15 (F) but is increased at P30 (H). Scale bar is 500 μm (A–D) and 100 μm (E–H).