Application of Fah knockout mice in the hepatocyte transplantation and the pathological changes

Aim ：To investigate the pathological changes in NTBC［2-（2-nitro-4-trifluoro-methyl-benzoyl)-1，3 cyclohexanedione］-induced hepatic injury in mice and in the repopulation of adult hepatocytes in Fah^-/- mouse. Methods ：Autogenous hepatic injuries in Fah^-/- mice were induced by the treatment of NTBC.Injection of hepatocytes obtained from wild-type mice to spleen were transplanted into the Fah^-/- mice.Then，changes to body weight and the likelihood of the transplanted Fah^-/- mice，and hepatic immunohistochemistry were observed.In addition，pathological changes to liver damage induced by NTBC treatment were analyzed under HE-staining microscopy and electron microscopy. Results ：The surviving Fah^-/- mice subjected to hepatocyte transplantation were found to be healthy and in stable body weight.Liver repopulation reached to 90% in the 8th week.Repopulating hepatocytes caused no alteration to histological structure of the recipient liver，and subacute hepatic injury occurred in the Fah^-/- mice after NTBC treatment.Electronic microscopy observations indicated that necrosis in the hepatocytes occurred at early stage and that apoptosis gradually appeared.It was also shown both necrosis and apoptosis co-existed in the same samples of interest at the following stages of the induced liver injury. Conclusion ：Transplanted hepatocytes proliferated in Fah^-/- mice allow 90% of the hepatocytic repopulation.Repopulation renders normal hepatic function and structure in the recipient.Fah^-/- mice，as a model of liver repopulation，could be applicable in study of stem cell derived hepatic cells in transplantation assay.