LONG-TERM EXPRESSION OF THE HEPATITIS-B VIRUS CORE-E-PROTEIN AND X-PROTEIN DOES NOT CAUSE PATHOLOGICAL-CHANGES IN TRANSGENIC MICE

Background/Aims: Chronic infections with the human hepatitis B virus c an result in liver cirrhosis and primary hepatocellular carcinoma. The reasons for these long-term effects are unclear. The aim of this stud y was to generate transgenic mice expressing the HBV X- and c/e-gene u nder authentic and foreign promoter control and to test whether the re spective gene products can cause pathologic effects during the lifespa n of a mouse. Moreover, the temporal and the tissue-specific regulatio n of the crucial HBV c/e-gene promoter was analyzed. Methods: Eight tr ansgenic mouse lines were generated. Four contained the c/e- and X-gen e and two contained only the X-gene under authentic promoter control. Two lines expressed only the X-gene under control of the rat insulin p romoter/enhancer. Gene expression was tested by protein and mRNA analy ses. During an observation period of 2 years, mice were sacrificed and organs subjected to histologic examination. Mice expressing the X-gen e in pancreatic beta cells were tested for the development of diabetes . Results: In the liver, slight histopathologic alterations but no neo plastic changes could be observed in mice expressing the X-gene. Activ ity of the c/e-gene promoter/enhancer was age dependent and was not re stricted to hepatocytes. Conclusion: No evidence was obtained that lon g-term expression of the HBV c/e- and X-gene products can cause neopla sia during the lifespan of a mouse.