| Project/Area Number |
26461296
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Research Field |
Neurology
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| Research Institution | Kyoto Prefectural University of Medicine |
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Principal Investigator |
Mizuta Ikuko 京都府立医科大学, 医学(系)研究科(研究院), 助教 (80397760)
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| Co-Investigator(Kenkyū-buntansha) |
山口 政光 京都工芸繊維大学, 応用生物学系, 教授 (00182460)
水野 敏樹 京都府立医科大学, 医学(系)研究科(研究院), 教授 (30264782)
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| Project Period (FY) |
2014-04-01 – 2018-03-31
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| Project Status |
Completed (Fiscal Year 2017)
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| Budget Amount *help |
¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000)
Fiscal Year 2016: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2015: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2014: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000)
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| Keywords | 脳小血管病 / ショウジョウバエ / Notch / 遺伝性脳小血管病 / 疾患モデル |
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| Outline of Final Research Achievements |
This study aimed to make Drosophila (fruit fly) model of cerebral small vessel diseases by overexpression of Notch3. Notch3 is a homologous gene of fly Notch, and the causative gene for CADASIL, the most common hereditary cerebral small vessel disease. It is known that excess Notch signaling causes rough eye phenotype in Drosophila. However, overexpression of Notch3 showed little effect, suggesting Notch3 had no signaling function in fly. To address this issue, we made constructs of chimeric Notch3 and chimeric JAG1, a ligand of Notch3. CADASIL mutations localize in EGF-like repeats of Notch3. Chimeric Notch3 was prepared by exchange between regions excluding EGF-like repeats of human Notch3 and those of Drosophila Notch. Chimeric JAG1 was prepared in the similar way. The co-overexpression of chimeric Notch3 and chimeric JAG1 resulted in the rough eye phenotype. Use of the chimeric proteins may be initial step to make the disease model of fly.
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