Development of Disease Model Mice for Parvovirus-Related Disorder and Pathogenic Mechanism

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To elucidate pathogenic mechanisms on parvovirus-related disorder, functions of parvoviral NS and P4 promoter which regulate to expression of NS were examined in vitro and in vivo experiments. The results are as follows.1) CRE on P4 region was important role in its promoter activity, and CREB and/or certain trans-activation factor was suggested to be required to activation of P4 promoter as cellular factors especially in tumor cells. Since Spermatocytes-specific EGFP expression was demonstrated in transgenic mice that express EGFP under P4 promoter, cellular factors that enhance P4 activity seemed to be in spermatocytes.2) Transgenic mice that expected to tetracycline-inducible NS over-expression was developed. However, non-specific leaky expression of NS was observed in these mice.3) The NS-transfected cell with retrovirus vector showed several phenotypic changes such as enhanced cell adherence, increased numbers of micro-villi, sensitivity to apoptosis and decreased tumorgenecity, and was induced epigenetic modification, histone-acetylation in CNTFR α gene. It suggested that a possibility of epigenetic modification with parvovirus NS should be related to parvovirus pathogenesis and its anti-tumor activity.4) New diagnosis method for parvovirus infection was developed using sequence information of mouse parvovirus in this study.