| Project/Area Number |
13210119
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| Research Category |
Grant-in-Aid for Scientific Research on Priority Areas
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| Allocation Type | Single-year Grants |
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| Review Section |
Biological Sciences
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| Research Institution | Osaka City University |
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Principal Investigator |
MORI Hiroshi Osaka City University, Graduate School of Medical Sciences, Professor, 大学院医学研究科, 教授 (10159189)
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| Co-Investigator(Kenkyū-buntansha) |
TOMIYAMA Takami Osaka City University, Graduate School of Medical Sciences, Lecturer, 大学院医学研究科, 講師 (10305633)
TAKUMA Hiroshi Osaka City University, Graduate School of Medical Sciences, Research associate, 大学院医学研究科, 助手 (00326258)
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| Project Period (FY) |
2001 – 2004
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| Project Status |
Completed (Fiscal Year 2004)
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| Budget Amount *help |
¥56,000,000 (Direct Cost: ¥56,000,000)
Fiscal Year 2004: ¥13,000,000 (Direct Cost: ¥13,000,000)
Fiscal Year 2003: ¥13,000,000 (Direct Cost: ¥13,000,000)
Fiscal Year 2002: ¥16,000,000 (Direct Cost: ¥16,000,000)
Fiscal Year 2001: ¥14,000,000 (Direct Cost: ¥14,000,000)
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| Keywords | Neuroscience / Dementia / splicing / neurodegeneration / tau / exon 10 / tauopachy / 脳・神経 / 老化 / タウ蛋白 |
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| Research Abstract |
Neurofibrillary tangles are the main brain pathological changes beside amyloid plaques in Alzheimer's disease and common in various dementia diseases referred to as tauopachy that include the same or similar changes of tau proteins. TAU gene is independently capable to cause some dementia such as FTDP-17, indicating that TAU gene encodes the major and causative. Although much variation family lines of FTDP- 17 are discovered, the majority of the disease was caused by the abnormalities in splicing of exon 10. We took out the genome fragment including exon 10 in interest from humans and extensively characterized and advocated the new mechanism about exon O splicing.
Differently from two models proposed by Hutton and Schellenberg groups, our new model was proposed based on the double stem loop structure. In our model, it was suggested that the 2nd stem loop further in a down stream of intron 10 controlled exon 10 splicing cooperatively with the conventional first stem loop in a negatively regulation manner. Moreover, in order to see the splicing control based on this model in not only culture cells but also brain tissue, we made the transgenic mice. It proved that all the decisive information for an isoform change during development in the present DNA construct. Based on this new model, we think that the essential cause of tauopachy including a phase of Alzheimer's disease is not in tau protein itself, but in the abnormalities of a splicing mechanism that influences an expression of exon 10.
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