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 是锚定在神经元外表面以及较小程度上锚定在淋巴细胞中的宿主蛋白。引起痒病的传染性病原体（PrP^<Sc>）被认为是 PrP^c 的改良形式。然而，PrP^c 在正常未感染动物中的作用仍不清楚。在这里，我们描述了一种新型心肌病小鼠模型，该模型是在朊病毒剂易感转基因（Tg）小鼠的发育过程中观察到的。这些 Tg 小鼠在其组织中选择性表达 OrPrP，如 mRNA RT-PCR、蛋白质印迹和免疫组织化学所示。 OrPrP 在心脏中表达高水平，在骨骼肌中表达中等水平，在脑中表达低水平，在肺、肝、脾、肾和胸腺中几乎检测不到水平。有趣的是，这些小鼠的心电图显示，心肌收缩明显延长，QRS间期异常。此外，组织学研究显示心肌中存在多个胞质内空泡。这些数据提示心脏中OrPrP的高表达可能导致心脏异常。此外，注射阿托品后，这些Tg小鼠的心电图波形出现异常。因此，这些小鼠可能提供一种新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.

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)。

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)

Shyu.W.C., Onodera.T.: "Molecular modulation of expression of prion protein by heart shock"Mol. Neuro-Bid.. 26(1). 1-12 (2002)

Shyu.W.C.，Onodera.T.：“心脏休克对朊病毒蛋白表达的分子调节”Mol。