• Search Research Projects
  • Search Researchers
  • How to Use
  1. Back to previous page

Molecular genetic analysis of familial amyloidotic polyneuropathy

Research Project

Project/Area Number 63440082
Research Category

Grant-in-Aid for General Scientific Research (A)

Allocation TypeSingle-year Grants
Research Field Human genetics
Research InstitutionKUMAMOTO UNIVERSITY

Principal Investigator

YAMAMURA Ken-ichi  Kumamoto Univ., Med. School, Professor, 医学部, 教授 (90115197)

Co-Investigator(Kenkyū-buntansha) TASHIRO Fumi  Kumamoto Univ., Med. School, Assistant Professor, 医学部, 助手 (40136213)
MIYAZAKI Jun-ichi  Kumamoto Univ., Med. School, Associate Professor, 医学部, 助教授 (10200156)
Project Period (FY) 1988 – 1989
Project Status Completed (Fiscal Year 1989)
Budget Amount *help
¥2,100,000 (Direct Cost: ¥2,100,000)
Fiscal Year 1989: ¥2,100,000 (Direct Cost: ¥2,100,000)
KeywordsFamilial amyloidotic polyneuropathy / Transthyretin / Transgenic mouse / Amyloid / Serum amyloid P component / トランスジェニックマウス / 家族性アミロイドポリニューロパシー
Research Abstract

Familial amyloidotic polyneuropathy (FAP) is an autosomal dominant disorder characterized by extracellular deposition of amyloid fibrils and by prominent peripheral and autonomic nerve involvement. Although the gene responsible for this disease has been identified as the transthyretin (TTR) gene and well characterized at molecular level, many questions, such as the mechanism of amyloid deposition, remain to be elucidated. We formerly produced two lines of transgenic mice by introducing the human mutant TTR gene containing its own promoter (0.6-hTTR30) or metallothionein promoter (MT-hTTR30). In these two lines the total serum concentrations of human mutant TTR were the same. However, the onset of amyloid deposition in MT-hTTR30 lines was 6 months of age and was 9 months earlier than that in the 0.6-hTTR30 lines. These results suggest that the concentration of homo-tetramers composed of human mutant TTR but not the total amount of human mutant TTR molecule is important for amyloid deposition.
To analyze the role of the human serum amyloid P component (SAP) which is a minor component of amyloid fibrils, we also produced SAP transgenic mice. Interestingly, the serum levels of human SAP were roughly proportional to the number of copies integrated and were higher than that of the human serum in three lines. These mice were mated with MT-hTTR30 transgenic to obtain mice carrying both genes. In these mice the onset of amyloid deposition was not accelerated suggesting that human SAP is not involved in the initiation of amyloid deposition.
Strangely enough, there were no amyloid deposits in peripheral nervous tissues where amyloid deposition is commonly observed in FAP patients. These results suggest that the production of mutant TTR molecule in the chorid plexus or high level expression is required for the amyloid deposition in these tissues.

Report

(3 results)
  • 1989 Annual Research Report   Final Research Report Summary
  • 1988 Annual Research Report
  • Research Products

    (15 results)

All Other

All Publications (15 results)

  • [Publications] Iwanaga,T.,Yamamura,K.,et al.: "Liver-specific and high-level expression of human serum amyloid P component gene in transgenic mice" Dev.Genet.10. 365-371 (1989)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1989 Final Research Report Summary
  • [Publications] Shimada,K.,Yamamura,K.,et al.: "Transgenic mouse model of familial amyloidotic polyneuropathy" Mol.Biol.Med.6. 333-343 (1989)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1989 Final Research Report Summary
  • [Publications] Yamamura,K.,Shimada,K.,et al.: "Production of a transgenic mouse model for a human dominantly inherited disease" Pure and Applied Chemistry(in press).

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1989 Final Research Report Summary
  • [Publications] S.Wakasugi: "An autosomal dominant mutation of facial development in a transgenic mouse" Dev. Genet. 9. 203-212 (1988)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1989 Final Research Report Summary
  • [Publications] K.Yamamura: "Expression of tissue-specific genes in transgenic mice" Cell Different. Dev. 25:(suppl) 47-52, 1988.

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1989 Final Research Report Summary
  • [Publications] T.Murakami: "Tissue-and developmental stage-specific expression of the rat arnithine carbamoyl transferase gene in transgenic mice" Dev. Genet. 10:393-401, 1989.

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1989 Final Research Report Summary
  • [Publications] T.Iwanaga: "Liver-specific and high-level expression of human serum amyloid P component gene in transgenic mice" Dev. Genet. 10:365-371, 1989.

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1989 Final Research Report Summary
  • [Publications] J.Miyazaki: "Expression vector system based on the chicken beta-actin promoter directs high-level production of interleukin-5" Gene 79:269-277, 1989.

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1989 Final Research Report Summary
  • [Publications] K.Shimada: "Transgenic mouse model of familial amyloidotic polyneuropathy" Mol. Biol. Med. 6:333-343, 1989.

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1989 Final Research Report Summary
  • [Publications] Iwanaga,T.,Yamamura,K.,et al.: "Liver-specific and high-level expression of human serum amyloid P component gene in transgenic mice" Dev.Genet.10. 365-371 (1989)

    • Related Report
      1989 Annual Research Report
  • [Publications] Shimada,K.,Yamamura,K.,et al.: "Transgenic mouse model of familial amyloidotic polyneuropathy" Mol.Biol.Med.6. 333-343 (1989)

    • Related Report
      1989 Annual Research Report
  • [Publications] Yamamura,K.,Shimada,K.,et al.: "Production of a transgenic mouse model for a human dominantly inherited disease" Pure and Applied Chemistry.

    • Related Report
      1989 Annual Research Report
  • [Publications] Wakasugi,S.;Iwanaga,T.;Inomoto,T.;Tengan,T.;Maeda,S.;Uehira,M.;Araki,K.;Miyazaki,J.;Eto,K.;Shnada,K.;Tamamura,K.: Dev.Genet.9. 203-212 (1988)

    • Related Report
      1988 Annual Research Report
  • [Publications] Yamamura,K.;Wakasugi,S.;Iwanaga,T.;Inomoto,T.;Maeda,S.;Shimada,K.: Cell Diff.Dev.25(Suppl). 47-52 (1988)

    • Related Report
      1988 Annual Research Report
  • [Publications] Iwanaga,T.;Wakasugi,S.;Inomoto,T.;Uehira,M.;Ohnishi,S.;Nishiguchi,S.;Araki,K.;Uno,M.;Miyazaki,J.;Maeda,S.;Shimada,K.;Yamamura,K.: Dev.Genet.

    • Related Report
      1988 Annual Research Report

URL: 

Published: 1989-04-01   Modified: 2016-04-21  

Information User Guide FAQ News Terms of Use Attribution of KAKENHI

Powered by NII kakenhi