| Project/Area Number |
07557183
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| Research Category |
Grant-in-Aid for Scientific Research (A)
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| Allocation Type | Single-year Grants |
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| Section | 展開研究 |
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| Research Field |
General anatomy (including Histology/Embryology)
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| Research Institution | ASAHIKAWA MEDICAL COLLEGE (1997)
Osaka University (1995-1996) |
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Principal Investigator |
KIYAMA Hiroshi Asahikawa Medical College, Professor, 医学部, 教授 (00192021)
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| Co-Investigator(Kenkyū-buntansha) |
TSUDA Manabu Tanabe Pharmaceutical, Researcher, 応用生化学研究所, 研究員
IMAIZMI Kazunori Tanabe Pharmaceutical, Researcher, 応用生化学研究所, 研究員
TAGA Tetsuya Osaka Univ., Inst.Cell Biol., Research Associate, 助手 (40192629)
KATO Hidemasa Asahikawa Medical College, Research Associate, 医学部, 助手 (50292123)
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| Project Period (FY) |
1995 – 1997
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| Project Status |
Completed (Fiscal Year 1997)
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| Budget Amount *help |
¥5,700,000 (Direct Cost: ¥5,700,000)
Fiscal Year 1997: ¥2,700,000 (Direct Cost: ¥2,700,000)
Fiscal Year 1996: ¥3,000,000 (Direct Cost: ¥3,000,000)
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| Keywords | GAP-43 / transgenic / hypoglossal / adenovirus / nerve injury / regeneration / Ras / LacZ / LacZ / 発現抑制 / 神経軸索再生 / キーワード / p53 / IL-6マップキナーゼ / トランスジェニック動物 |
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| Research Abstract |
In order to investigate functional significance of molecules which are associated with nerve regeneration, we have designed a conditional loss of function using transgenic strategy. To achieve this, GAP-43 promoter was cloned, and this promoter was used to allow expression of antisense mRNA or ribozyme of certain mRNA when nerve got injury. GAP-43/LacZ fusion protein was used as a reporter to examine the promoter specificity. After several trials, GAP-43/LacZ transgene whose expression was driven by GAP-43 promoter was obtained. The expression pattern of GAP-43/LacZ fusion protein was very similar to that of native GAP-43. Since the N-terminus of GAP-43 can be a targeting signal toward growth cone, LacZ staining was observed in nerve terminal. Therefore this transgenic animal would be very useful for further analys of plasticity and regeneration. In addition, we have also established adenovirus mediated gene transfer system which could be a great advantage for the manipulation of a certain gene expression. Using this adenovirus system, a functional significance of Ras signaling pathway during nerve regeneration was accessed. At the moment, we are trying to lose function of Ras after nerve injury using dominant-negative Ras and Ras-GAP 1m adenovirus which we have already made. The analysis using these adenovirus vectors are now under going.
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