Figure 9.

Comparison of the effect of keratin overexpression or mutation in the pancreas and liver. The schematic contrasts the effect of mutant/absent, normal (basal), and forced keratin expression with the effects of such expression on pancreatic and liver injury. Keratin mutation or absence (schematic, left) is well tolerated in the pancreas but predisposes to significant injury in the liver.9 As would be expected, normal keratin expression does not lead to pancreas/liver injury (schematic, middle). In contrast, forced K8/K18 expression as we observed in the graded keratin overexpression in the K8 and K8/K18 transgenic mice promotes progressive parallel injury in the pancreas without having a clearly discernible effect in the liver (schematic, right). The most severe form of pancreatic injury is reflected by the likely overwhelming pancreatic keratin overexpression reported by Casanova and colleagues.19