2000 Fiscal Year Final Research Report Summary
Molecular neurobiological analyses of Huntington's disease model mouse
| Project/Area Number |
11680767
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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 |
Neurochemistry/Neuropharmacology
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| Research Institution | Fujita Health University |
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Principal Investigator |
ISHIGURO Hiroshi Fujita Health University, Inst.for Comprehensive Med.Sci., Associate Professor, 総合医科学研究所, 助教授 (20211039)
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| Co-Investigator(Kenkyū-buntansha) |
YAMADA Kouji Fujita Health University, Inst.for Comprehensive Med.Sci., Research Assistant, 総合医科学研究所, 研究技術員 (60278306)
NISHII Kazuhiro Fujita Health University, Inst.for Comprehensive Med.Sci., Research Assistant, 総合医科学研究所, 研究技術員 (50278305)
SAWADA Hirohide Fujita Health University, Inst.for Comprehensive Med.Sci., Research Associate, 総合医科学研究所, 助手 (30247663)
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| Project Period (FY) |
1999 – 2000
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| Keywords | Huntington's disease / CAG repeat / mosaicism / model mouse / striatum |
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| Research Abstract |
Huntington's disease (HD) is an autosomal dominant neurodegenerative disorder characterized by involuntary movement, personality change, and dementia. We have generated HD gene knock-in mice in which the exon 1 of the mouse HD gene was replaced by the human exon 1 containing 77CAG repeats. Wild and mutated huntingtin proteins were expressed ubiquitously in brain and peripheral tissues. To determine the number of CAG repeats, genescan-analysis was performed using genomic DNA prepared from various tissues. Instability of CAG repeats through meiotic transmission is considered to be implicated in their expansion and a mouse identified with 97 CAG repeats in exon 1 of mouse HD gene was mated with homozygous (77 CAG repeat, male) and normal mice (female). In addition, a one or two CAG repeat expansion was found in 25% of the litters from paternal transmission. The CAG repeat in 20% litters, by contrast, was contracted by maternal transmission. Expanded CAG repeat instability (somatic CAG mosaicism) in 30 week-old mice was found in brain except for the cerebellum, and in peripheral organs such as the liver, kidney and stomach. We confirmed the same results of expanded CAG repeat instability in human brain of HD patients. The CAG repeat instability of this mouse model may mirror the abnormalities in HD patients.
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