| Project/Area Number |
14360175
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Basic veterinary science/Basic zootechnical science
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| Research Institution | The University of Tokyo |
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Principal Investigator |
ONODERA Takashi The University of Tokyo, Graduate School of Agricultural and Life Sciences, Professor, 大学院・農学生命科学研究科, 教授 (90012781)
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| Co-Investigator(Kenkyū-buntansha) |
MATSUMOTO Yoshitsugu The University of Tokyo, Graduate School of Agricultural and Life Sciences, Associate Professor, 大学院・農学生命科学研究科, 助教授 (00173922)
SAEKI Keiichi The University of Tokyo, Graduate School of Agricultural and Life Sciences, Assistant, 大学院・農学生命科学研究科, 助手 (10311630)
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| Project Period (FY) |
2002 – 2004
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| Project Status |
Completed (Fiscal Year 2004)
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| Budget Amount *help |
¥16,800,000 (Direct Cost: ¥16,800,000)
Fiscal Year 2004: ¥4,900,000 (Direct Cost: ¥4,900,000)
Fiscal Year 2003: ¥4,900,000 (Direct Cost: ¥4,900,000)
Fiscal Year 2002: ¥7,000,000 (Direct Cost: ¥7,000,000)
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| Keywords | prion / BSE / CWD / Western blot / ELISA / RT-PCR / scrapie / myocardiopathy |
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| Research Abstract |
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.
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