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Analysis of the mechanism of misfolding to amyloid protein using mouse amyloidosis

Research Project

Project/Area Number 11470056
Research Category

Grant-in-Aid for Scientific Research (B).

Allocation TypeSingle-year Grants
Section一般
Research Field Experimental pathology
Research InstitutionShinshu University

Principal Investigator

HIGUCHI Keiichi  Shinshu University, Medicine, professor, 医学部, 教授 (20173156)

Co-Investigator(Kenkyū-buntansha) NAIKI Hironobu  Fukui medical University, Medicine, Professor, 医学部, 教授 (10227704)
MORI Masayuki  Shinshu University, Medicine, Lecturer, 医学部, 講師 (60273190)
Project Period (FY) 1999 – 2000
Project Status Completed (Fiscal Year 2000)
Budget Amount *help
¥13,700,000 (Direct Cost: ¥13,700,000)
Fiscal Year 2000: ¥2,700,000 (Direct Cost: ¥2,700,000)
Fiscal Year 1999: ¥11,000,000 (Direct Cost: ¥11,000,000)
Keywordsamyloidosis / mouse / apoA-II / transmission / misfolding / fibril formation / environment / genetics / in situ hybridization
Research Abstract

We studied mouse AApoAII amyloidosis to elucidate the common mechanism of valious amyloidosis. We obtained the following results,
1)We found transmission of amyloidosis from old amyloid laden mice to young mice by eating feces of old mice.
2)Injection of amyloid fibrils induced amyloidosis in normal and amyloidosis resistant mice.
3)In situ hybridization analysis revealed that extra-hepatic synthesis of apoA-II may contribute amyloid fibril formation in the local tissues.
4)We studied the induction of AApoAII amyloidosis by various kind of amyloid fibrils. All amyloid fibrils injected intravenously into mice induced amyloidosis. Injected amyloid fibrils settle to amyloidogenic tissues(the lungs, tongue, stomach ets.)and might act as template(seed)for amyloid fibril formation.
5)Acceleration of amyloidosis was observed in R1.P1-Apoa2c mice born from the mother mice in which severe amyloidosis was induced by AApoAII injection.
6)We found severe amyloidosis in C57BL mice with amyloid-resistant type A apoA-II reared in one animal center and no amyloid deposition in R1.P1-Apoa2c mice with amyloidogenic type C apoA-II reared in SPf condition.
7)We tried to develop the therapeutic methods for amyloidosis. Injection of adeno-virus with amyloid resistant apoA-II cDNA, food containing safflower oil as a lipid inhibited amyloidosis in vivo and anti-oxidant(rifanpicine and NDGA)inhibited fibril formation in vivo.
These results suggested that invasion of exogenous substances with amyloid-fibril-like structures may act as seeds and trigger the conformational change of endogenous amyloid protein to polymerize into amyloid fibril.
Mouse amyloidosis is a good model for study of the relationship between genetic and environmental factors in pathology of diseases.

Report

(3 results)
  • 2000 Annual Research Report   Final Research Report Summary
  • 1999 Annual Research Report
  • Research Products

    (63 results)

All Other

All Publications (63 results)

  • [Publications] Higuchi Keiichi: "Senescence-accelerated mouse."Methods Enzymol. 309:. 674-686 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Chiba Takuya: "Mouse senile amyloid deposition is suppressed by adenovirus-mediated overexpression of amyloid-resistant apolipoprotein A-II."Am J Pathol. 155. 1319-1326 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Xia Chen: "Genetic typing of the senescence-accelerated mouse(SAM)strains with microsatellite markers."Mamm Genome. 10. 235-238 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Shimizu Motoyuki: "Identification of peak bone mass QTL in a spontaneously osteoporotic mouse strain."Mamm Genome. 10. 81-87 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Mori Masayuki: "Deletion in the beige gene of the beige rat owing to recombination between LINE1s."Mamm Genome. 10. 692-695 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Takeda Norikazu: "Expression of the c-fos gene induced by parathyroid hormone in the bones of SAMP6 mice, a murine model for senile osteoporosis."Mech Ageing Dev. 108. 87-97 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Hirosawa Hiromi: "Aminoguanidine supplementation delays the onset of senescence in vitro in dermal fibroblast-like cells from senescence-accelerated mice."J Gerontol A Biol Sci. 54A. B276-282 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Wang Jing: "Wild type ApoA-II gene does not rescue Senescence-accelerated mouse(SAMP1)from short life span and accelerated mortality."J Gerontol B Biol Sci. 55A. B432-439 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] ZhanJun Guo: "Genetic analysis of lifespan in hybrid progeny derived from the SAMP1 mouse strain with accelerated senescence."Mechanisms of Ageing & Development. 118. 435-444 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Nishikawa Tomofumi: "Tubular aggregates in the skeletal muscle of the senescence-accelerated mouse ; SAM."Mech Ageing Dev. 114. 89-99 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Umezawa Makiko,: "Serum lipid concentrations and mean life span are modulated by dietary polyunsaturated fatty acids in the Senescence-accelerated mouse"J Nutr. 130. 221-227 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Yazaki Masahide: "Cardiac amyloid in patients with familial amyloid polyneuropathy consists of abundant wild-type transthyretin."Biochem Biophys Res Commun. 274. 702-706 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Shoji Masato,: "Related Articles Senile ocular amyloidosis in SAM and BALB/c strains of mice."Mech Ageing Dev. 120. 87-94 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Kikuchi Takanobu: "Molecular cloning and characterization of a new neuron-specific homologue of rat polypyrimidine tract binding protein."J Biochem(Tokyo),. 128. 811-821 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Mori Masayuki: "Spontaneous loss-of-function mutations of the 8-oxoguanine DNA glycosylase gene in mice and exploration of the possible implication of the gene in senescence."Free Rad Biol Med. (印刷中). (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Xing Yanming: "Transmission of mouse senile amyloidosis. 2001"Lab Invest. (印刷中). (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Fu Li: "Extra-hepatic expression of apolipoprotein A-II mRNA revealed by in situ hybridization analysis ; possible contribution to mouse senile amyloidosis."J Histochem Cytochem. (印刷中). (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Mizutani Junichi: "Unique mutation in mitochondrial DNA of Senescence-Accelerated Mouse(SAM)strains."J Heredity. (印刷中). (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] 日本遺伝子治療学会: "遺伝子治療開発研究ハンドブック"エヌ・ティー・エス. 1061 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] 折茂肇: "新老年学(第2版)"東京大学出版会. 1595 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Robert A Kyle: "Amyloid and Amyloidosis 1998"Parthenon Publishing.. 585 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Gilles Grateuau: "Les Amyloidoses"Flammarion Medicine Science. 580 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] 永田和宏、森正敬、吉田賢右: "分子シャペロンによる細胞機能制御"シュプリンガー・フェアラーク東京(印刷中). (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] 永田和宏: "分子生物学・免疫学キーワード辞典(第2版)"医学書院(印刷中). (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Chiba t, Kogishi K, Wang J, Xia C, matsushita T, Miyaziaki J, Saito I, Hosokawa M, Higuchi K: "Mouse senile amyloid depsition is suppressed by adenobirus-mediated overexpression of amyloid-resistant apolipoprotein A-II."Am J Pathol. 155. 1319-1326 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Xia C, Higuchi K, Shimizu M, Matsushita T, kogishi K, Wang J, Chiba T, Festinng MF, Hosokawa M: "Genetic typing of the senescence-acclerated mouse(SAM)strains with microsatellite markers."Mamm Genome. 10. 235-238 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 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, mstusihta M, Okamura H, Sekikawa T, Nakamura T, Johnson TE, Hosokawa M: "Identification of peak bone mass QTL in a spontaneously osteoporotic mouse strain."Mamm Genome. 10. 81-87 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Higuchi K, Hosokawa M, Takeda T: "Senescence-accelerated mouse."Methods Enzymol. 309. 674-686 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Takeda N, tsuboyama T, Kasai R, Takahashi K, Shimizu M, Nakamura T, Higuchi K, Hosokawa M: "Expression of the c-fos gene induced by parathyroid hormone in the bones of SAMP6 mice a murine model for senile osteoporosis."Mech Ageing Dev. 108. 87-97 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Fujikawa H, Nishikawa T, Zhu BH, Nishimura Y, Shimizu M, Kimoto M, Higuchi K, Hosokawa M: "Aminoguanidine supplementaiton delays the onset of senescence in vitro in dermal fivroblast-like cells from senescence-acclerated mice."J Gerontol A Biol Sci Med Sci. 54. B276-82 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Mori M, Nishikawa T, Higuchi K, Nishimura M: "Deletion in the beige of the beige gene rat owing to recombination between LINE1s."Mamm Genome. 10. 692-695 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Wang J.Matsushita T, Kogishi K, Xia C, Ohta A, Chiba T, Nakamura A, Kondo H, Mori M, Hosokawa M, Higuchi K: "Wild type ApoA-II gene does not rescue Senescence-accelerated mouse(SAMP1)from short life span and accelerated mortality."J Gerontol B Biol Sci. 55A. B432-439 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Guo Z, Toichi E, Hosono M, Hosokawa T, Hosokawa M, Higuchi K, Mori M: "Genetic analysis of lifespan in hybrid porgeny derived from the SAMP1 mouse strain with accelerated senescence."Mech Ageing Dev. 118. 35-44 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Nishikawa T, Takahashi JA, Matsushita T, Ohnishi K, Higuchi K, Hashimoto N, Hosokawa M: "Tubular aggregates in the skeletal muscle of the senescence-accelerated mouse ; SAM."Mech Ageing Dev. 114. 89-99 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Umezawa M, Takeda T, Kogishi K, Higuchi K, Matushita T, Wang J.Chiba T, Hosokawa M: "Serum lipid concentrations and mean life span are modulated by dietary polyunsaturated fatty acids in the Senescence-accelerated mouse."J Nutr. 130. 221-227 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Yazaki M, Tokuda T, Nakamura A, Higashikata T, Koyama J, Higuchi K, Harihara Y, Baba S, Kametani F, Ikeda S: "Cardiac amyloid in patients with familial amyloid polyneuropathy consists of abundant wild-type transthyretin."Biochem Biophys Res Commun. 274. 702-706 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Kikuchi T, Ichikawa M, Arai J.Tateiwa H, Fu L, Higuchi K, Yoshimura N: "Molecular cloning and characterizatrion of a new neuron-specific homelogue of rat polypyrimidine tract binding protein."J Biochem(Tokyo). 128. 811-821 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Shoji M, Mtsushita T, Higuchi K, Honda Y, Hosokawa M: "Related Articles Senile ocular amyloidosis in SAM and BALB/c strains of mice."Mech Ageing Dev. 120. 87-94 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Xing Y, Nakamura A, Takuya Chiba, Kumiko Kogishi, Takatoshi Matsushita, Fu Li, Zhanjun Guo, Masanori Hosokawa, Masayuki Mori, Keiichi Higuchi: "Transmission of mouse senile amyloidosis."Lab Invest. (in press). (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Mori M, Toyokuni S, Kondoh S, Naiki H, Toichi E, Hosokawa M, Higuchi K: "Spontaneous loss-of-function mutations of the 8-oxoguanine DNA glycosylase gene in mice and exploration of the possible implication of the gene in senescence."Free Rad Biol Med. (in press). (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Shoji Masato: "Related Articles Senile ocular amyloidosis in SAM and BALB/c strains of mice."Mech Ageing Dev. 120. 87-94 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Wang Jing: "Wild type ApoA-II gene does not rescue Senescence-accelerated mouse (SAMP1 ) from short life span and accelerated mortality."J Gerontol B Biol Sci. 55A. B432-439 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] ZhanJun Guo: "Genetic analysis of lifespan in hybrid progeny derived from the SAMP1 mouse strain with accelerated senescence."Mechanisms of Ageing & Development. 118. 435-444 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Nishikawa Tomofumi: "Tubular aggregates in the skeletal muscle of the senescence-accelerated mouse ; SAM."Mech Ageing Dev. 114. 89-99 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Umezawa Makiko: "Serum lipid concentrations and mean life span are modulated by dietary polyunsaturated fatty acids in the Senescence-accelerated mouse"J Nutr. 130. 221-227 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Yazaki Masahide: "Cardiac amyloid in patients with familial amyloid polyneuropathy consists of abundant wild- type transthyretin."Biochem Biophys Res Commun. 274. 702-706 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Kikuchi Takanobu: "Molecular cloning and characterization of a new neuron-specific homologue of rat polypyrimidine tract binding protein."J Biochem(Tokyo),. 128. 811-821 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Xing Yanming: "Transmission of mouse senile amyloidosis.2001"Lab Invest. (印刷中). (2001)

    • Related Report
      2000 Annual Research Report
  • [Publications] Mori Masayuki: "Spontaneous loss-of-function mutations of the 8-oxoguanine DNA glycosylase gene in mice and exploration of the possible implication of the gene in senescence."Free Rad Biolo Med. (印刷中). (2001)

    • Related Report
      2000 Annual Research Report
  • [Publications] 樋口京一: "老化促進モデルマウス(SAM)"信州医誌. 48. 7-14 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] 中村明宏: "老化モデル動物の性差"Geriatric Medicine. 38. 1833-1836 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Fu Li: "Extra-hepatic expression of apolipoprotein A-II mRNA revealed by in situ hybridization analysis ; possible contribution to mouse senile amyloidosis."J Histochem Cytochem. (印刷中). (2001)

    • Related Report
      2000 Annual Research Report
  • [Publications] Gilles Grateuau: "Les Amyloidoses"Flammarion Medicine Science. 580 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] 永田和宏: "分子生物学・免疫学キーワード辞典(第2版)"医学書院(印刷中). (2001)

    • Related Report
      2000 Annual Research Report
  • [Publications] 永田和宏,森正敬,吉田賢右: "分子シャペロンによる細胞機能制御"シュプリンガー・フェアラーク東京(印刷中). (2001)

    • Related Report
      2000 Annual Research Report
  • [Publications] Chiba Takuya: "Mouse senile amyloid deposition is suppressed by adenovirus-mediated overexpression of amyloid-resistant apolipoprotein A-II."Am J Pathol 1999. 155・4. 1319-1326 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Ffujisawa Hiromi: "Aminoguanidine supplementation delays the onset of senescence in vitro in dermal fibroblast-like cells from senescence-accelerated mice."J Gerontol A Biol Sci Med Sci. 54・7. B276-B282 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Mori Mnasaayuki: "Deletion in beige gene of the beige rat owing to recombination between LINE1s."Mamm Genome. 10・7. 692-695 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Higuchi Keiichi: "Senescence-accelerated mouse."Methods Enzymol. 309. 674-686 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Xia Chen: "Genetic typing of the senescence-accelerated mouse (SAM) strains with microsatellite markers."Mamm Genome. 10・3. 235-238 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Sshimizu Motoyuki: "Identification of peak bone mass QTL in a spontaneously osteoporotic mouse strain."Mamm Genome. 10・2. 81-87 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] 日本遺伝子治療学会: "遺伝子治療開発研究ハンドブック"エヌ・ティー・エス. 1061 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] 折茂 肇: "新老年学(第2版)"東京大学出版会. 1595 (1999)

    • Related Report
      1999 Annual Research Report

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Published: 1999-04-01   Modified: 2016-04-21  

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