2001 Fiscal Year Final Research Report Summary
Elucidation of pathogenesis in CAG-repeat diseases using DNA chip
| Project/Area Number |
12670601
|
|---|
| Research Category |
Grant-in-Aid for Scientific Research (C)
|
| Allocation Type | Single-year Grants |
|---|
| Section | 一般 |
|---|
| Research Field |
Neurology
|
|---|
| Research Institution | Nagoya University |
|---|
Principal Investigator |
DOYU Manabu Graduate School of Medicine, Nagoya University, Assistant Professor, 大学院・医学研究科, 講師 (90293703)
|
|---|
| Co-Investigator(Kenkyū-buntansha) |
SOBUE Gen Graduate School of Medicine, Nagoya University, Professor, 大学院・医学研究科, 教授 (20148315)
INUKAI Akira University Hospital, Nagoya University, Assistant Professor, 医学部・附属病院, 助手 (30314016)
|
|---|
| Project Period (FY) |
2000 – 2001
|
| Keywords | CAG repeat disease / polyglutamine tract / neuronal cell death / Spinal and bulbar muscular atrophy / adenovirus vector / In vitro neuronal cell culture model / DNA chip / Gene expression analysis |
|---|
| Research Abstract |
CAG-repeat diseases are inherited neurodegenerative diseases caused by the expansion of CAG repeats in the disease causing genes. The pathogenesis of CAG-repeat diseases remains to be elucidated. In this study, we tried to identify CAG repeat disease-related genes which are involved with neurodegeneration in CAG-repeat diseases. We made in vitro CAG-repeat disease neuronal culture model using adenovirus vectors, which expressed expanded or normal CAG repeat (polyglutamine tract) in human neuroblastoma (SH-SY5Y). This model showed increasing of nuclear aggregates after infection, axonal atrophy and decreasing of cellular activity detected with MTS assay. Further DNA chip analysis (including about 10,000 genes ) revealed upregulation of a gene associated with neurite outgrowth in expanded polyglutamine-expressed group, followed by confirmation with quantitative real time RT-PCR (Taqmann probe PCR). This finding is matched with axonal atrophy observed in CAG-repeat disease animal model.
|
Research Products
(20 results)
