1999 Fiscal Year Final Research Report Summary
Production of transgenic mice expressing familial AD relevant genes
| Project/Area Number |
10680697
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Nerve anatomy/Neuropathology
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| Research Institution | TOHOKU UNIVERSITY |
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Principal Investigator |
SHIN Ryong-woon school of medicine Lecturer 1996〜1197 Tohoku University, 大学院・医学系研究科, 講師 (40271910)
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| Project Period (FY) |
1998 – 1999
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| Keywords | Alzheimer's disease / presenilin 1 / amyloid precursor protein / transgenic mouse / processing / animal model |
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| Research Abstract |
This study is dedicated to establish an experimental animal model which allows to demonstrate the cascade that missense mutation in presenilin 1 gene identified as causative gene for the majority of familial Alzheimer's disease (FAD) leads to the phenotype of Aβ deposition, one of the pathological lesions of AD, and to provide a tool for analysis of processing of proteins involved in the cascade. For this purpose we attempted to produce trasgenic mice which express FAD relevant proteins. We have produced Tg mice which express wild type human PS1(wtPS1) protein and those which express missense PS1 (codon 146 Met → Val), one of the missense mutations shown to increase the production of Aβ1-42. In addition, we have produced Tg mice which express mutant APP at codon 717(London type of FAD). We have produced polyclonal antibodies generated against N-terminal 1 to 81 amino acid sequence and C-terminal 299 to 407 amino acids sequence, both of which were fused to GST. Using these tools we will analyze the mechanism involved in the deposition of Aβ. There have been reports showing that mutant APP Tg mice generate Aβ deposits in the brain with aging (after 1.5years), whereas mutant PS1 Tg mice fail to generate Aβ deposits in the brain. To demonstrate "the seeding hypothesis for Aβ deposition", young APP 717 Tg mice and M146V PS1 Tg mice are subjected to intracranial administration of Aβ peptide. We will see whether the injected material in these animals serve as a seed for accelerated deposition of endogenous murine Aβ.
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[Publications] lino K,Sasano H,Oki Y,Andoh N,Shin R-W,Kitamoto T,Totsune K,Takahashi K,Suzuki H,Nagura H,Yoshimi T.: "Urocortin expression in human central nervous system"Clin Endocrinol. 50. 107-114 (1998)
Description
「研究成果報告書概要(和文)」より
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[Publications] Iino K, Sasano H, Oki Y, Andoh N, Shin R-W, Kitamoto T, Totsune K, Takahashi K, Suzuki H, Nagura H, Yoshimi T.: "Urocortin expression in human central nervous system."Clin Endocrinol. 50. 107-114 (1998)
Description
「研究成果報告書概要(欧文)」より
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