[Core protein of hepatitis C virus expressed in transgenic mice is associated with the expression of Fas molecule].

Hepatitis C virus (HCV) is a leading cause of morbidity and mortality worldwide but the pathogenesis of liver cell injury and the molecular mechanism of persistent infection of HCV are not well understood. The aim of this work is to establish the animal model of HCV infection for studying the biosynthesis and pathogenesis of HCV structural protein in transgenic mice. The structural genes (C+ E1 + E2) and 5'-uncoding region gene (5'UCR) of HCV isolated from China was inserted into pcDNA3 vector. The transgenic mice were produced by microinfecting this plasmid into mouse (C57BL/6 x ICR) embryos and the integrated mice were identified. The expression of core protein of HCV and mFas molecule were confirmed by immunohistochemical analysis using monoclonal antibody. The results revealed that the expression of core protein was detected in many mouses' tissues with nuclear staining, while the heart tissue was with cytoplasmic staining. The expression level in tissues was indicated as: heart>lung>kidney>liver. At meantime, Fas molecule was detected in heart, kidney and liver tissues, and the expression of Fas was parallel to that of core protein. Transgenic mouse containing HCV structural gene was established and the expression of Fas molecule may be associated with the expression of core protein of HCV. The Fas system or other signaling pathway to the programmed cell death may play important roles in HCV infection. Our transgenic mouse will provide a useful animal model to critically address issues of immune pathogenesis, direct cytopathic potential and carcinogenesis of the structural protein of HCV.