Generation and analysis of transgenic mice carrying parvoviral NS gene

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Parvoviruses have small single stranded DNA,its nonstructural (NS) protein regulates viral capsid protein (VP) and host gene expressions. Correlation between parvoviruses and autoimmun diseases or antitumorigenesis suspected because of modification of immunocompetence. Thus, we tried to generate transgenic mice to involve modification of autoimmune disease and anti tumorigenesis with parvoviral NS protein.At first, tetracycline inducible gene expression system was applied to generate transgenic mice overexperssing prvoviral NS,because of potential cytotoxicity of NS to mouse fetus. We generated 4 founder mice carrying reverse tetracycline transactivator (rtTA) gene and 3 founder mice carrying fusion transgene including tetracycline responsive element (TRE) and parvoviral NS genes. These mice are cross breeding to generate dual transgenic mice overexpression NS by administration of tetracycline.On the other hand, we also examined cytotoxicity of NS and cellular factors interact with NS in host cells, to expect phenotypes by overexpression of NS.The results indicate that cytotoxicity of NS is correlated with induction of apoptosis, and that NS interacts to CBP (CREB binding protein) which is an important coactivators to bind several transcriptional factors.