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

细小病毒相关疾病模型小鼠的建立及其发病机制

• 批准号: 15300139
• 负责人: YAGAMI Ken-ichi
• 金额: $ 10.62万
• 依托单位: University of Tsukuba
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (B)
• 财政年份: 2003
• 资助国家: 日本
• 起止时间: 2003 至 2005
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-15300139/
• 关键词: Parvovirus; NS; P4 promoter; Transgenic mice; Epigenetics; Histone acetylation; 精子形成; 病態モデルマウス; マウス; 病態モデル

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.

为了阐明细小病毒相关疾病的致病机制，在体外和体内实验中检查了细小病毒NS和调节NS表达的P4启动子的功能。结果如下：1)P4区的CRE对其启动子活性起重要作用，认为CREB和/或某些反式激活因子作为细胞因子尤其是肿瘤细胞中P4启动子的激活是必需的。由于在P4启动子下表达EGFP的转基因小鼠中证实了精母细胞特异性EGFP表达，因此增强P4活性的细胞因子似乎存在于精母细胞中。2)开发了预期四环素诱导的NS过表达的转基因小鼠。然而，在这些小鼠中观察到NS的非特异性渗漏表达。3)逆转录病毒载体转染NS的细胞表现出细胞粘附增强、微绒毛数量增加、细胞凋亡敏感性和致瘤性降低等表型变化，并诱导表观遗传修饰、CNTFRα基因组蛋白乙酰化。提示细小病毒NS表观遗传修饰的可能性与细小病毒的发病机制及其抗肿瘤活性有关。4)本研究利用小鼠细小病毒的序列信息开发了细小病毒感染的新诊断方法。

项目成果

Parvovirus nonstructural proteins induce an epigenetic modification through histone acetylation in host genes and revert tumor malignancy to benignancy

• DOI: 10.1128/jvi.79.14.8886-8893.2005
• 发表时间: 2005-07-01
• 期刊: JOURNAL OF VIROLOGY
• 影响因子: 5.4
• 作者: Iseki, H;Shimizukawa, R;Yagami, K
• 通讯作者: Yagami, K

実験動物の微生物モニタリングマニュアル

实验动物微生物监测手册

• 发表时间: 2005
• 作者: 高倉彰;八神健一;山田靖子;大橋弘明
• 通讯作者: 大橋弘明

Parvovirus NS induces an epigenetic modification through histone acetylation in host genes and reverts tumor malignancy to benignancy.

细小病毒 NS 通过宿主基因中的组蛋白乙酰化诱导表观遗传修饰，并将肿瘤恶性肿瘤恢复为良性。

• 发表时间: 2005
• 期刊: J.Virol. 79
• 作者: Hisamoto;N.;Moriguchi;T.;Urushiyama;S.;Mitani;S.;Shibuya;H.;Matsumoto;K.;Iseki H
• 通讯作者: Iseki H

Development of ELISA using recombinant antigens for specific detection of mouse parvovirus infection.

开发使用重组抗原特异性检测小鼠细小病毒感染的 ELISA。

• 发表时间: 2006
• 期刊: Exp.Anim. 55(2)
• 作者: Zacharia J;Hillier C;Tanoue A;Tsujimoto G;Daly CJ;McGrath JC;Macdonald A.;國田 智;Satoshi Kunita;國田 智;Satoshi Kunita;Satoshi Kunita
• 通讯作者: Satoshi Kunita

A Manual for Microbiological Monitoring on Laboratory Rodents

实验室啮齿动物微生物监测手册

• 发表时间: 2005
• 作者: Takakura A;Yagami K;Yamada Y;Ohhashi H.
• 通讯作者: Ohhashi H.