| Project/Area Number |
17390111
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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 |
Experimental pathology
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| Research Institution | Shinshu University |
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Principal Investigator |
HIGUCHI Keiichi Shinshu University, Graduate School of Medicine, Professor (20173156)
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| Co-Investigator(Kenkyū-buntansha) |
MORI Masayuki Shinshu University, Graduate School of Medicine, Associate Professor (60273190)
SAWASHITA Jinko Shinshu University, Graduate School of Medicine, Assistant Professor (40359732)
MAEDA Shuichiro University of Yamanashi, Interdisciplinary Graduate School of Medicine and Engineering, Professor (10117244)
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| Project Period (FY) |
2005 – 2007
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| Project Status |
Completed (Fiscal Year 2007)
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| Budget Amount *help |
¥15,630,000 (Direct Cost: ¥14,400,000、Indirect Cost: ¥1,230,000)
Fiscal Year 2007: ¥5,330,000 (Direct Cost: ¥4,100,000、Indirect Cost: ¥1,230,000)
Fiscal Year 2006: ¥4,400,000 (Direct Cost: ¥4,400,000)
Fiscal Year 2005: ¥5,900,000 (Direct Cost: ¥5,900,000)
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| Keywords | Model animals / Amyloidosis / Transmission / Mouse / Inflammation / Fibril conformation / ApoA-II / Dialysis / モデルマウス / AApoAII / FAP / AAアミロイドーシス / 透析アミロイドーシス |
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| Research Abstract |
The amyloidosis is a group of protein misfolding disorders characterized by the accumulation of amyloid fibrils formed from a variety of proteins that, under normal physiological conditions, are harmless and soluble. Here we investigate into the pathogenesis of the transmission/infection of amyloidosis using newly developed animal models of amyloidosis. We used mouse models for AApoAII amyloidosis, ATTR (familial amyloid polyneuropathy; FAP) amyloidosis, AA(reactive) amyloidosis, AB2M (dialysis) amyloidosis and cheetah AA amyloidosis. We developed a new transgenic mouse strain, Apoa2^cTg, Apoa2^c/c which over-expressed amyloidogenic Apoa2^c gene. These strain mice showed very high susceptibility to the injection of exogenous amyloid fibrils. AA amyloidosis is one of the principal causes of mortality in captive cheetahs (Acinonyx jubatus), which are in danger of extinction, We found that show the feces from a cheetah with AA amyloidosis can act as a possible origin to accelerate the transmission of AA amyloidosis. We also tried to induce amyloidosis by the injection of ATTR amyloid fibrils in the transgenic mouse strain (TTRMet30rg, mTtr-/-) which expressed TTR variant of FAP patients. We found that seeding/transmission effect of the amyloid fibrils was not obvious in ATTR deposition in the tissues, but deposition of other amyloid fibrils (ex. AApoAII or AA) induced ATTR deposition. We developed a new transgenic mouse strain (hβ2MTg+/+, mβ2m-/-) which over-expresses human β2 microglobulin (β2M), and is deficient in endogenous β2m gene. Up to date, Aβ2M deposition could not be detected even after the induction by injection with Aβ2M amyloid fibrils. We found that over-expression of heat shock proteins prevented development of AApoAII amyloidosis using HSF1 (heat shock factor 1) transgenic mice. We also investigated the effect of inflammation on amyloidosis using interleukin 6 deficient mice.
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