Long-term expression of the hepatitis B virus core-e- and X-proteins does not cause pathologic changes in transgenic mice
| Autor: | Hans-Peter Pudollek, Eva Maria Schmitteckert, Kurt Reifenberg, H J Schlicht, Gabriele Spindler, Jürgen Löhler, Josef Köck |
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| Rok vydání: | 1997 |
| Předmět: |
Gene Expression Regulation
Viral Genetically modified mouse Transgene Mice Transgenic Biology medicine.disease_cause Hepatitis B Antigens Islets of Langerhans Mice Gene expression medicine Animals Humans Hepatitis B e Antigens Promoter Regions Genetic Enhancer Regulation of gene expression Hepatitis B virus Hepatology biology.organism_classification medicine.disease Hepatitis B Core Antigens Virology Molecular biology Enhancer Elements Genetic Hepadnaviridae Organ Specificity Hepatocellular carcinoma |
| Zdroj: | Journal of Hepatology. 26:119-130 |
| ISSN: | 0168-8278 |
| DOI: | 10.1016/s0168-8278(97)80018-9 |
| Popis: | Background/Aims: Chronic infections with the human hepatitis B virus can result in liver cirrhosis and primary hepatocellular carcinoma. The reasons for these long-term effects are unclear. The aim of this study was to generate transgenic mice expressing the HBV X- and c/e-gene under authentic and foreign promoter control and to test whether the respective gene products can cause pathologic effects during the lifespan of a mouse. Moreover, the temporal and the tissue-specific regulation of the crucial HBV c/e-gene promoter was analyzed. Methods: Eight transgenic mouse lines were generated. Four contained the c/e- and X-gene and two contained only the X-gene under authentic promoter control. Two lines expressed only the X-gene under control of the rat insulin promoter/enhancer. Gene expression was tested by protein and mRNA analyses. During an observation period of 2 years, mice were sacrificed and organs subjected to histologic examination. Mice expressing the X-gene in pancreatic beta cells were tested for the development of diabetes. Results: In the liver, slight histopathologic alterations but no neoplastic changes could be observed in mice expressing the X-gene. Activity of the c/e-gene promoter/enhancer was age dependent and was not restricted to hepatocytes. Conclusion: No evidence was obtained that long-term expression of the HBV c/e- and X-gene products can cause neoplasia during the lifespan of a mouse. |
| Databáze: | OpenAIRE |
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