Reduction of cytochemical ecto-ATPase activities in keratin 8-deficient FVB/N mouse livers.
Keratin 8 (K8) and keratin 18 are the intermediate filament proteins that are expressed in hepatocytes. A K8-deficient FVB/N mouse is a unique animal model for assessing the contribution of keratin intermediate filaments (IFs) to the structural and functional integrity of hepatocytes. Hepatocytes from homozygous (-/-) K8-deficient mice manifest a reduced bile acid secretion and an increased fragility to mechanical stress and hepatotoxic drugs. Hepatocytes from heterozygous (+/-) mice are more susceptible to drug-induced injury. Immunofluorescent microscopy revealed that hepatocytes from (+/-) mice maintained K8 IFs and F-actin that are similar to those in wild-type (+/+) mouse hepatocytes. In (-/-) mouse hepatocytes, K8 protein was negative and F-actin presented a coarse and irregular pattern. Ecto-ATPase, detected by enzyme histochemistry and observed by electron microscopy, was reduced in the bile canaliculi of both (+/-) and (-/-) mouse livers, in comparison with that of (+/+) mouse livers. These results reveal for the first time different microscopical findings regarding the livers of these three genotypes. They also suggest that the reduction of ecto-ATPase plays a role in the increased fragility of (+/-) and (-/-) mouse livers.
Satoh
M.I.
MI
Département de chimie-biologie, Université du Québec à Trois-Rivières, C.P.500 Trois-Rivières, Québec, Canada G9A 5H7. Monique_Cadrin@uqtr.uquebec.ca
Hovington
Hélène
H
Cadrin
M.
M