research for highly sensitive assay for BSE agents

BSE 因子高灵敏度测定研究

• 批准号: 14360175
• 负责人: ONODERA Takashi
• 金额: $ 10.75万
• 依托单位: The University of Tokyo
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (B)
• 财政年份: 2002
• 资助国家: 日本
• 起止时间: 2002 至 2004
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-14360175/
• 关键词: prion; BSE; CWD; Western blot; ELISA; RT-PCR; scrapie; myocardiopathy

PrP^c is a host protein anchored to the outer surface of neurons and to a lesser extent in lymphocytes. The transmissible agent (PrP^<Sc>) responsible for scrapie is thought to be a modified form of PrP^c. However, the role of PrP^c in normal uninfected animals is still unknown. Here we describe a novel mouse model for cardiomyopathy, which was observed during the development of prion agent susceptible transgenic (Tg) mouse. These Tg mice were shown to selectively express OrPrP in their tissues, as demonstrated by RT-PCR for mRNA, Western blotting and immunohistochemistry. High levels of OrPrP expression were seen in heart, medium levels in skeletal muscle, low levels in brain, and barely detectable levels in lung, liver, spleen, kidney and thymus. Interestingly, the electrocardiogram of these mice showed that cardiac muscle contraction was significantly prolonged with abnormality of the QRS interval. In addition, the histologic study showed multiple intracytoplasmic vacuolation in the heart muscle. These data suggest that the high expression of OrPrP in heart may cause the cardiac abnormality. Furthermore, an abnormal waveform of ECG was observed in these Tg mice after atropine injection. These mice therefore may be possible to provide a new model to elucidate experimental cardiomyopathy.

PrP^c是一种宿主蛋白，定位于神经元的外表面，少量存在于淋巴细胞中。引起瘙痒病的传播因子(PrP^&lt；SC&gt；)被认为是PrP^c的一种改良形式。然而，PrP^c在正常未感染动物中的作用仍不清楚。在此，我们描述了一种新的心肌病小鼠模型，该模型是在Pron试剂敏感的转基因(TG)小鼠发育过程中观察到的。RT-PCR、Western blotting和免疫组织化学结果表明，这些转基因小鼠的组织中有选择性地表达OrPrP。OrPrP在心脏中高水平表达，在骨骼肌中中等水平表达，在脑中低水平表达，在肺、肝、脾、肾和胸腺中几乎检测不到。有趣的是，这些小鼠的心电图显示，随着QRS间期的异常，心肌收缩显著延长。此外，组织学检查显示心肌内有多个胞浆内空泡化。提示心脏组织中OrPrP的高表达可能是心脏异常的原因之一。此外，注射阿托品后，这些转基因小鼠出现了异常的心电波形。因此，这些小鼠可能提供一种新的模型来阐明实验性心肌病。

项目成果

Octapeptide repeat region and N-terminal half of hydrophobic region of prion protein (PrP) mediates PrP-dependent activation of superoxide dismutase.

八肽重复区和朊病毒蛋白 (PrP) 疏水区的 N 端一半介导超氧化物歧化酶的 PrP 依赖性激活。

• 发表时间: 2005
• 期刊: Biochem Biophys.Res.Commun. 326
• 作者: Sakudo;A.;Onodera;T.
• 通讯作者: T.

Infection Route-Independent Accumulation of Splenic Abnormal Prion Protein

脾脏异常朊病毒蛋白的感染途径独立积累

• 发表时间: 2005
• 期刊: Jpn.J.Infect.Dis. 58
• 作者: Y.Inoue;Y.Yamakawa;A.Sakudo;T.Kinumi;Y Nakamura;Y.Matsumoto;K.Saeki;T.Kamiyama;T.Onodera;M.Nishijima
• 通讯作者: M.Nishijima

Kubosaki A, Onodera T: "Expression of normal cellular prion protein T lymphocytes, and effect of copperion"Biochem.Biopys.Res.Commun.. 307. 810-813 (2003)

Kubosaki A、Onodera T：“正常细胞朊病毒蛋白 T 淋巴细胞的表达和铜离子的作用”Biochem.Biopys.Res.Commun.. 307. 810-813 (2003)

小野寺 節: "現場でのBSE対策"食品衛生研究. 52(2). 23-32 (2002)

Setsu Onodera：“现场 BSE 对策”食品卫生研究 52(2) (2002)。

小野寺 節: "プリオンの測定法について"Organ Biology. 9(3). 7-13 (2002)

Setsu Onodera：“测量朊病毒的方法”器官生物学9(3)(2002)。