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Studies of the Pathogenesis of Amyloidosis : Verification of the Hypothesis 'Transmission of Abnormal Proteins Structure' Using Mouse Senile Amyloidosis.

Research Project

Project/Area Number 09670224
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Experimental pathology
Research InstitutionSHINSHU UNIVERSITY (1998)
Kyoto University (1997)

Principal Investigator

HIGUCHI Keiichi  Shinshu University School of Medicine・Research Center on Aging and Adaptation., Professor, 医学部・加齢適応研究センター, 教授 (20173156)

Co-Investigator(Kenkyū-buntansha) HOSOKAWA Masanori  Kyoto University・Institute for frontier Medical Sciences, Associate Professor, 再生医科学研究所, 助教授 (00127135)
Project Period (FY) 1997 – 1998
Project Status Completed (Fiscal Year 1998)
Budget Amount *help
¥3,000,000 (Direct Cost: ¥3,000,000)
Fiscal Year 1998: ¥1,300,000 (Direct Cost: ¥1,300,000)
Fiscal Year 1997: ¥1,700,000 (Direct Cost: ¥1,700,000)
Keywordsamyloidosis / fibrilization / transmission / mouse / apoA-II / AApoAII / polymerize / aging / 繊維形成反応 / pro-apoA-II
Research Abstract

Amyloidosis refers to a group of diseases characterized by tissue deposition of amyloid fibrils. A single intravenous injection of a very small amount of the native mouse senile amyloid fibrils (AApoAII) induced severe systemic amyloid deposition in young mice having the amyloidogenic apoA-II gene (Apoa2^c). After AApoAII injection, amyloid deposition occurred rapidly, and advanced in an accelerated manner observed in spontaneous senile amyloidosis in mice. However, the injection of denatured AApoAII, native apoA-II in high density lipoprotein (HDL) and denatured apoA-II monomer which have the same primary structure but without a fibril conformation did not induce amyloidosis. These findings suggested that the nucleation-dependent polymerization found in vitro also occurs in vivo, and that the fibril conformation is required for the injected amyloid fibrils to act as seeds in viva.
We injected AApoAII amyloid fibrils isolated from the liver of an old R1.P1-Apoa2^c mouse into the stomach … More of young mice using feeding needles for five consecutive days. After 2 months, all mice had AApoAII deposits in the lamina propria of the small intestine. Amyloid deposition extended to the tongue, stomach, heart and liver at 3 and 4 months after feeding. AApoAII suspended in drinking water also induced amyloidosis. Amyloid deposition was induced in young mice reared in the same cage for three months with old mice that had severe amyloidosis. Detection of AApoAII in feces of old mice suggested the transmission by eating of feces.
Fibril conformation-dependent fibrillization is proposed as a general model of the pathogenesis of various kinds of amyloidosis occurring in viva. Further, we substantiated the transmissibility of AApoAII amyloidosis and presented the unique pathogenesis of amyloidosis "oral transmission of amyloid fibril conformation", that is, invasion of exogenous amyloid fibrils acts as seeds and changes the conformation of endogenous amyloid protein to polymerize into amyloid fibrils. Less

Report

(3 results)
  • 1998 Annual Research Report   Final Research Report Summary
  • 1997 Annual Research Report
  • Research Products

    (48 results)

All Other

All Publications (48 results)

  • [Publications] Keiichi Higuchi: "The Senescence-Accelerated Mouse" Meth.Enzym.印刷中. (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Keiichi Higuchi: "Fibrilization in mouse senile amyloidosis is fibril conformation dependent" Lab.Invest.78・12. 1535-1542 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Hiromi Fujisawa: "Accelerated aging of dermal fibroblast-like cells from Senescence Accelerated Mouse(SAM):Acceleration of changes in DNA ploidy associated with in-vitro cellular aging." J.Gerontol.53A・1. B11-B17 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Masato Shoji: "A morphological and morphometrical study of the retina in aging SAM mice." Opthal.Res.30・1. 172-179 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Jingxian Han: "Age-related changes in blood pressure in Senescence-Accelerated Mouse(SAM);aged SAMP1 mice manifest hypertensive vascular diseases." Lab.Anim.Sci.48・1. 97-104 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] 樋口京一: "老化促進モデルマウス(SAM)を用いた長寿科学への分子的アプローチ" Molecular Medicine. 35・5. 608-615 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] 折茂 肇: "新老年学(第2版)" 東京大学出版会, 1648 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] 日本遺伝子治療学会: "遺伝子治療開発ハンドブック" エヌ・ティー・エヌ 印刷中, (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Wang J,Kitagawa K,Kitado H,Kogishi K,Matshushita T.Hosokawa M,Higuchi, K: "Regulation of the metabolism of plasma lipoproteins by apolipoprotein A-II." Biochem.Biophys.Acta.1345. 248-258 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Higuchi K,Kogishi K,Wang J,Xia C,Chiba T,Matsushita T,Hosokawa M: "Accumulation of pro-apolipoprotein A-II in mouse senile amyloid fibrils." Biochem.J.325. 653-659 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Hoshii Y,Kawano H,Cui, D,Takeda T,Gondo T,Takahashi M,Kogishi K,Higuchi K,Ishihara T.: "Amyloid A protein amyloidosis induced in apolipoprotein-E deficient mice." Am.J.Pathol.151. 911-917 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Toichi E,Hanada K,Hosokawa T,Higuchi K,Hosokawa M,Imamura S,Hosono M.: "Age-related decline in humoral immunity caused by the selective loss of TH cells and decline in cellular immunity caused by the impaired migration of inflammatory cells with out a loss of TDTH cells in SAMP1 mice." Mech.Ageing Dev.99. 199-218 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Fujisawa H,Seriu N,Zhu B-H,Higuchi K,Hosokawa M.: "Inheritance and strain distribution of a persistent hyaloid vascular system in mice." Exp.Eye Res.64. 553-558 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Ueno M,Akiguchi I,Hosokawa M,Shinnou M,Sakamoto H,Takemura M,Higuchi K: "Age-related changes in the brain transfer of blood-borne horseradish peroxidase in the hippocampus.." Acta.Neuropathol. 93. 233-240 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Ueno M,Akiguchi I,Hosokawa M,Shinnou M,Sakamoto H,Takemura M,Higuchi K.: "Age-related changes in the barrier function in mouse brain II Accumulation of serum albumin in the olfactory bulb of SAM mice increased with aging." Arch.Gerontol.Geriatr.25. 321-331 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Fujisawa H,Nishikawa T,Zhu B-H,Takeda N,Jujo H,Higuchi K,Hosokawa M.: "Accelerated aging of dermal fibroblast-like cells from Senescence Accelerated Mouse (SAM) : Acceleration of changes in DNA ploidy associated with in-vitro cellular aging." J.Gerontol.53A. B11-B17 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Shoji M,Okada M,Ohta A,Higuchi K,Hosokawa M,Honda Y.: "A morphological and morphometrical study of the retina in aging SAM mice.." Opthal.Res.30. 172-179 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Han XS,Hosokawa M,Umezawa M,Yagi H,Matsushita T,Higuchi K,Takeda T.: "Age-related changes in blood pressure in Senescence-Accelerated Mouse (SAM) ; aged SAMP1 mice manifest hypertensive vascular diseases." Lab.Anim.Sci.48. 97-104 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Higuchi K,Kogishi K,Wang J,Xia C,Chiba T,Matsushita T,Hoshii Y,Kawano H,Ishihara T,Yokota T,Hosokawa M.: "Fibrilization in mouse senile amyloidosis is fibril conformation-dependent." Lab.Invest.78. 1535-11542 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Nishikawa T,Takahashi JA,Fujibayashi Y,Fujisawa H,Zhu B,Nishimura Y,Ohnishi K,Higuchi K,Hashimoto N,Hosokawa M: "An early stage mechanism of the age-associated mitochondrial dysfunction in the brain of SAMP8 mice ; an age-associated neurodegeneration animal model." Neurosci.Lett. 254. 69-72 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] kawamata T,Akiguchi I,Maeda K,Tanaka C,Higuchi K,Tech.Hosokawa M,Takeda T.: "Age-related changes in the brains of senescence-accelerated mice (SAM) : association with glial and endothelial reactions." Microsc.Res.43. 59-67 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Ueno M,Akiguchi I,Hosokawa M,Shinnou M,Sakamoto H,Takemura M,Higuchi K.: "Ultrastructural and permeability features of microvessels in the olfactory bulbs of SAM mice." Acta Neuropathol. (Berl). 96. 261-270 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Higuchi K,Hosokawa M,Takeda T: "The Senescence-Accelerated Mouse." Meth.Enzym.(in press). (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Mori M,Higuchi K,Nishimura M.: "Deletion in the beige gene of the beige rat due to recombination between LINE1s." Mamm.Genome. (in press). (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Xia C,Higuchi K,Shimizu M,Matsushita T,Kogishi K,Wang J,Chiba T,Festing MFW,Hosokawa M.: "Genetic typing of the Senescence-Accelerated Mouse (SAM) strains with maicrosatellite markers." Mamm.Genone. (in press). (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Shimizu M,Higuchi K,Bennett B,Xia C,Tsuboyama T,Kasai S,Chiba T,Fujisawa H,Kogishi K,Kitado H,Kimoto M,Takeda N,Mastushita M,Okumura H,Serikawa T,Nakamura T,Johnson TE and Hosokawa M.: "Identification of peak bone mass QTL in a spontaneously osteoporotic mouse strain." Mamm.Genome. (in press). (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Higuchi K.: "Genetic characterization of Senescence Accelerated Mouse (SAM)" Exp.Gerontol.32. 129-138 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Takeda T,Hosokawa M,Higuchi K.: "Senescence-Accelerated Mouse (SAM) : A novel murine model of senescence." Exp.Gerontol.32. 105-110 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Hosokawa M,Umezawa M,Higuchi K,Takeda T.: "Intervention of senescence in SAM mice." J.Anti-Aging Med.1. 1-11 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Takeda T,Higuchi K,Hosokawa M.: "Senescence-accelerated Mouse (SAM) : with special reference to development and pathological phenotypes.." ILAR Journal. 38. 109-117 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Higuchi Keiichi: "Senescence model of amyloidosis. In Amyloidosis, Benson, M.D.ed" Flamarion Press Paris. (in press). (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Higuchi Keiichi: "Amyloidosis.in New Gerontology Orimo, Hajime, ed" Tokyo University press. (in press). (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Keiishi Higuchi: "The Senescence-Accelerated Mouse" Meth.Enzym.印刷中. 印刷中 (1999)

    • Related Report
      1998 Annual Research Report
  • [Publications] Keiichi Higuchi: "Fibrilization in mouse senile amyloidosis is fibril conformation dependent" Lab.Inveset.78・12. 1535-1542 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Hiromi Fujisawa: "Accelerated aging of dermal fibroblast-like cells from Senescence Accelerated Mouse (SAM) : Acceleration of changes in DNA ploidy associated with in-viro cellular aging." J.Gerntol.53A・1. B11-B17 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Masato Shoji: "A morphological and morphometrical study of the retina in aging SAM mice." Opthal. Res.30・1. 172-179 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Jingxian Han: "Age-related changes in blood pressure in Senescence-Accelerated Mouse (SAM) ; aged SAMP1 mice manifest hypertensive vascular diseases." Lab.Anim.Sci.48・1. (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] 樋口京一: "老化促進モデルマウス(SAM)を用いた長寿科学への分子的アプローチ" Molecular Medicine. 35・5. 608-615 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] 折茂 肇: "新老年学(第2版)" 東京大学出版会, 1648 (1999)

    • Related Report
      1998 Annual Research Report
  • [Publications] 日本遺伝子治療学会: "遺伝子治療開発ハンドブック" エヌ・ティー・エヌ(印刷中), (1999)

    • Related Report
      1998 Annual Research Report
  • [Publications] Higuchi K: "Accumulation of pro-apolipoprotein A-II in mouse senile amyloid fibrils." Biochem.J.325(3). 635-659 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Wang J: "Regulation of the metabolism of plasma lipoproteins by apolipoprotein A-II." Biochim Biophys Acts. 1345(3). 248-258 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Hishii Y: "Amyloid A protein amyloidosis induced in apolipoprotein E deficfent mice." Am.J.Pathol.151(4). 911-917 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Fujisawa H: "Accelerated aging of dermal fibroblast-like cells from Senescenc Accelerated Mouse (SAM)." J.Geronotol.53A(1). B11-B17 (1998)

    • Related Report
      1997 Annual Research Report
  • [Publications] Toichi E.: "Age-related decline humoral immunity caused by the selective lose of TH cells." Mech.Ageing Dev.(in press). (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Shoji M: "A morphological and morphometrical study of the retina in aging SAM mice." Orthal.Res.(in press). (1998)

    • Related Report
      1997 Annual Research Report
  • [Publications] 樋口京一: "新老年学(折茂肇編)「カミロイドーシス」" 東京大学出版(印刷中), (1998)

    • Related Report
      1997 Annual Research Report
  • [Publications] 樋口京一: "遺伝子治療開発研究ハンドブック(日本遺伝子治療学会編)「SAMモデル」" エヌ・ティー・エス(印刷中), (1998)

    • Related Report
      1997 Annual Research Report

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Published: 1997-04-01   Modified: 2016-04-21  

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