| Project/Area Number |
16390075
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
General medical chemistry
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| Research Institution | Nagoya University |
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Principal Investigator |
FURUKAWA Kouichi Nagoya University, Graduate School of Medicine, Professor, 大学院医学系研究科, 教授 (80211530)
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| Co-Investigator(Kenkyū-buntansha) |
URANO Takeshi Nagoya University, Graduate School of Medicine, Associate Professor, 大学院医学系研究科, 助教授 (70293701)
FURUKAWA Keiko Chubu University, College of life and health sciences, Professor, 生命健康科学部, 教授 (50260732)
TAJIMA Orie Chubu University, College of life and health sciences, Assistant Professor, 生命健康科学部, 講師 (10362237)
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| Project Period (FY) |
2004 – 2006
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| Project Status |
Completed (Fiscal Year 2006)
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| Budget Amount *help |
¥14,700,000 (Direct Cost: ¥14,700,000)
Fiscal Year 2006: ¥3,800,000 (Direct Cost: ¥3,800,000)
Fiscal Year 2005: ¥4,700,000 (Direct Cost: ¥4,700,000)
Fiscal Year 2004: ¥6,200,000 (Direct Cost: ¥6,200,000)
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| Keywords | knockout / glycolipid / nerve / neuron / degeneration / ganglioside / raft / inflammation / スフィンゴ糖脂質 / 神経変性 / グリア / 補体 / GD3 / 遺伝子発現 / アセチルコリン / セロトニン |
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| Research Abstract |
1. Analyses of double knockout (KO) mice of GM2/GD2synthase and GD3 synthase genes revealed nerve degeneration, skin lesions, anti-anxiety, reduced memory and learning, reduced sensory function, lower responsiveness of acetylcholine muscarinic receptor and increased sensitivity of serotonin 5-HT2 receptor, suggesting that acidic glycosphingolipids are essential in the maintenance of nervous tissues.
2. Gene expression profiling resulted in the identification of 5 genes reduced and 15 genes increased in the D-KO mice. In particular, complement factors and those receptors are up-regulated, indicating that dysfunction of complement-regulatory molecules in rafts and resulting tissue damages induced complement activation, leading to exacerbation of
3. deggnnertiion experiments of hypoglossal nerves showed reduced regenerative activity in the GM2/GD2synthase KO mice, Analysis of genes which are down-regulated in the hypoglossal nerve nuclei in the KO mice with LCM and RT-PCR revealed that expr
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ession of BDNF and GDNF etc are down-regulated, suggesting that GD3 may not be enough to compensate the lost function of asialo-series structures.
4. β4GalT-VI gene KO mice showed no changes in glycolipid composition, and lac-cer synthesis seemed to be performed with β4GaIT-V.
5. GM3 synthase gene KO mice were born and grew up with no apparent abnormality, suggesting the compensation effects with asialo-series glycolipids.
6. Gb3/CD77 synthase gene KO mice showed no sensitivity to verotoxins, suggesting its exclusive role in the response to the toxins.
To summarize, it has become possible to see through which aspects can be compensated by the remaining glycolipids and which ones not. In the future plan, following themes seem to be important. i.e. 1. analysis of roles of particular glycolipids based on the comparison of phenotypes between single gene KO and D-KO mice. 2. Identification of ligand molecules specific for particular glycolipid. 3. analysis of membrane microdomains in vivo where glycolipids play roles by forming clusters. Less
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