2007 Fiscal Year Final Research Report Summary
Investigation into the pathogenesis of amyloidosis using the newly developed animal models.
| 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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| Keywords | Model animals / Amyloidosis / Transmission / Mouse / Inflammation / Fibril conformation / ApoA-II / Dialysis |
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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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[Journal Article] Amyloidosis in transgenic mice expressing murine amyloidogenic apolipoprotein A-II (Apoa2^c)2007
Author(s)
Ge, F., Yao, J., Fu, X., Guo, Z., Yan, J., Zhang, B., Zhang, H., Tomozawa, H., Miyazaki, J., Jinko, Sawashita, J., Mori, M., Higuchi, K
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Journal Title
Lab Invest 87(2)
Pages: 633-643
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Cross-seeding and cross-competition in mouse apolipoprotein A-II amyloid fibrils (AApoAII) and protein A amyloid fibrils (AA)2007
Author(s)
Yan, I., Fu, X., Ge, F., Zhang, B., Yao, J., Zhang, H., Qian, J., Tomozawa, H., Naiki, H., Sawashita, J., Mori, M., Higuchi, K
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Journal Title
Am J Pathol 171(1)
Pages: 172-180
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Quantitative Trait Locus that Determines the Cross-sectional Shape of the Femur in SAMP6 and SAMP2 mice2007
Author(s)
Otsuki, B., Matsumura, T., Shimizu, M., Mori, M., Okudaira, S., Nakanishi, R., Higuchi, K., Hosokawa, M., Tsuboyama, T., Nakamura, T
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Journal Title
J Bone Miner Res 22(5)
Pages: 675-685
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Elucidation of molecular mechanism of amyloidosis : the present, future, and dream. (Japanese)2007
Author(s)
Goto, Y., Kuwata, K., Sekishima, Y., Tanaka, M., Naiki, H., Nagai, Y., Matsuzaki, K., Higuchi, K
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Journal Title
Cell Technology 26(2)
Pages: 181-1185
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Mouse senile amyloidosis : possible horizontal transmission in the mouse room2007
Author(s)
Fu, X., Korenaga, T., Yan, J., Ge, F., Zhan, B., Qian, J., Naiki, H., Sawashita, J., Mori, M., Higuchi, K
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Journal Title
in "XIth International Symposium on Amyloidosis". (Skinner M, Berk JL, Connors LH, Seldin DC eds) CRC Press Boca Raton, FL USA
Pages: 10-12
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Amyloidosis in the transgenic mice of mouse amyloidgenic apolipoprotein A-II (Apoa2^c)2007
Author(s)
Higuchi, K., Ge, F., Fu, X., Yao, J., Zhan, B., Zhan, H., Qian, J., Sawashita, J., Mori, M.
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Journal Title
in "XIth International Symposium on Amyloidosis". (Skinner M, Berk JL, Connors LH, Seldin DC eds) CRC Press Boca Raton, FL USA
Pages: 143-145
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Transmissibility of mouse AApoAII amyloid fibrils : inactivation by physical and chemical methods2006
Author(s)
Zhang, H., Sawashita, J., Fu, X., Korenaga, T., Yan, J., Mori, M., Higuchi, K
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Journal Title
FASEB J 20(7)
Pages: 1012-1014
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Reduced coenzyme Q10 supplementation decelerates senescence in SAMP1 mice2006
Author(s)
Yan, J., Fujii, K., Yao, J., Kishida, H., Hosoe, K., Sawashita, J., Takeda, T., Mori, M., Higuchi, K
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Journal Title
Exp Gerontol 41(2)
Pages: 130-140
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Transmission of amyloidosis in offspring of mice with A ApoAII amyloidosis2006
Author(s)
Korenaga, T., Yan, T., Sawashita, J., Matsusita, T., Naiki, H., Hosokawa, M., Mori, M., Higuchi, K., Fu, X
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Journal Title
Am J Pathol 168(3)
Pages: 898-906
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Lanosterol synthase mutations cause cholesterol deficiency-associated cataracts in the Shumiya cataract rat2006
Author(s)
Mori, M., Li, G., Abe, I., Nakayama, J., Guo, Z., Sawashita, J., Ugawa, T., Nishizono, Serikawa, T., Higuchi, K., Shumiya, S
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Journal Title
J Clin Invest 116(2)
Pages: 395-404
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Unexpectedly high incidence of visceral AA-amyloidosis in slaughtered cattle in Japan2005
Author(s)
Tojo, K., Tokuda, T., Hoshii, Y., Fu, X., Higuchi, K., Matsui, T.,Kametani, F., Ikeda, S
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Journal Title
Amyloid 12(2)
Pages: 103-108
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] A locus for eosinophilia in the MES rat is on Chromosome 192005
Author(s)
Li, G., Guo, Z., Higuchi, K., Kawakubo, M., Matsumoto, K., Mori, M
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Journal Title
Mamm Genome 16(7)
Pages: 516-523
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Transmission of Mouse AApoAII Amyloidosis by the Amyloid Fibrils ; Inhibitory Effects on Transmission by the Denaturation / Degradation of Amyloid Fibrils2005
Author(s)
Sawashita, J., Zhang, H., Fu, X., Korenaga, T., Mori, M., Higuchi, K
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Journal Title
In "Amyloid and Amyloidosis" (Grateau G, Kyle RA, Skinner M eds) CRC Press, Boca Raton USA
Pages: 457-459
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Transmission of Mouse AApoAII Amyloidosis from Mother to Pups2005
Author(s)
Korenaga, T., Fu, X., Mori, M., Sawashita, J., Naiki, H., Matsushita, T., Higuchi, K
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Journal Title
In "Amyloid and Amyloidosis" (Grateau G, Kyle RA, Skinner M eds.), CRC Press, Boca Raton USA
Pages: 460-462
Description
「研究成果報告書概要(欧文)」より
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[Presentation] 遺伝子解析2005
Author(s)
森 政之
Organizer
第20回老化促進モデルマウス研究協議会
Place of Presentation
東京
Year and Date
2005-07-30
Description
「研究成果報告書概要(和文)」より
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