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A Potential Animal Model for Familial Amyloidotic Polyneuropathy Through Introduction of Human Mutant Transthyretin Gene Into Mice

  • S. Wakasugi
  • T. Inomoto
  • S. Yi
  • M. Naito
  • M. Uehira
  • T. Iwanaga
  • S. Maeda
  • K. Araki
  • J. Miyazaki
  • K. Takahashi
  • K. Shimada
  • K. Yamamura
Chapter

Abstract

Familial amyloidotic polyneuropathy (FAP) has been identified in a number of kindreds of the world. FAP is an autosomal dominant disorder characterized by extracellular deposition of fibrillar amyloid protein and by prominent peripheral nerve involvement (1–4). This protein is mainly composed of TTR with a substitution of methionine for valine at position 30 in the FAP type I, as reported in Japan, Sweden and Portugal (5–7). This amino acid substitution is thought to lead to amyloid deposition. The human TTR gene has been cloned and well characterized at the molecular level (8, 9). All the FAP patients so far examined carry one mutant gene (10, 11). However in patients with FAP, the age at onset varies from 20 to 45 years. In addition the clinical syndrome is variable even among kindreds with the same genetic defect. These data suggest involvement of factor(s) other than the single nucleotide mutation in the TTR gene. To elucidate this factor(s) and to examine the pathological process of amyloid deposition, we have produced transgenic mice by microinjecting the cloned human mutant TTR gene into fertilized eggs of C57BL/6 mice.

Keywords

Transgenic Mouse Transgenic Line Amyloid Deposition Single Nucleotide Mutation Familial Amyloidotic Polyneuropathy 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

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Copyright information

© Springer Science+Business Media New York 1988

Authors and Affiliations

  • S. Wakasugi
    • 1
  • T. Inomoto
    • 1
  • S. Yi
    • 2
  • M. Naito
    • 2
  • M. Uehira
    • 1
  • T. Iwanaga
    • 1
  • S. Maeda
    • 3
  • K. Araki
    • 1
  • J. Miyazaki
    • 1
  • K. Takahashi
    • 2
  • K. Shimada
    • 3
  • K. Yamamura
    • 1
  1. 1.Institute for Medical GeneticsKumamoto University Medical SchoolKumamoto 862Japan
  2. 2.Second Department of PathologyKumamoto University Medical SchoolKumamoto 862Japan
  3. 3.Department of BiochemistryKumamoto University Medical SchoolKumamoto 862Japan

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