| Project/Area Number |
11680742
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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 | Osaka City University |
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Principal Investigator |
MORI Hiroshi Osaka City Univ. Medical School, Department of Neuroscience / proefssor, 医学部, 教授 (10159189)
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| Co-Investigator(Kenkyū-buntansha) |
SUZUKI Misao Kumamoto Univ. Center for Animal Resources and Development, Division of Transgenic Technology / Associate professor, 動物資源開発研究センター, 助教授 (60253720)
SAHARA Naruhiko Osaka City Univ. Medical School, Department of Neuroscience / research associate, 医学部, 助手 (40261185)
TOMIYAMA Takami Osaka City Univ. Medical School, Department of Neuroscience / lecturer, 医学部, 講師 (10305633)
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| Project Period (FY) |
1999 – 2000
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| Project Status |
Completed (Fiscal Year 2000)
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| Budget Amount *help |
¥3,700,000 (Direct Cost: ¥3,700,000)
Fiscal Year 2000: ¥1,000,000 (Direct Cost: ¥1,000,000)
Fiscal Year 1999: ¥2,700,000 (Direct Cost: ¥2,700,000)
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| Keywords | Alzheimer's disease / APP / Abeta, senile plaque / transgenic mouse / model / neurotoxicity / presenilin / プレセニリン / マルツハイマー病 |
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| Research Abstract |
Amyloid plaques and neurofibrillary tangles are neuropathological and molecular hallmarks for Alzheimer's disease (AD). Their presence is highly important to understand the etiology of the disease. Making model mice is undoubtedly crucial to examine the molecular mechanism how to develop plaque formation and cell death in cerebral tissues and to study a potent therapeutic drug. We tried to make a mouse that bears cerebral amyloid plaques by cross the mutated APP717 (referred to as London mutation) mouse and the mutated PS1 mouse. Both mutations were generated by PCR with human APP and PS1 cDNA templates. These two DNA constructs for transgenic mice were integrated in prion promoter plasmid vector (from Dr. D.Borchelt, Jonhs Hopkins Univ.). We succeeded in generate three lines of mice with human APP717 and two lines of mice with human mutated PS1. The lines were established to show their genetic and protein expression. Amyloid protein was exmained and established to show neurotoxicity using fetal hippocampal neurons derived from these mice. An antagonic effect was found to be associated with crystamine G that is an analogue of congo red to bind amyloid fibril in AD brain.
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