Investigation of cerebral small vessel diseases using Notch3 transgenic Drosophila

2017 Fiscal Year Final Research Report

• Project/Area Number: 26461296
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Neurology
• Research Institution: Kyoto Prefectural University of Medicine
• Principal Investigator: Mizuta Ikuko 京都府立医科大学, 医学(系)研究科(研究院), 助教 (80397760)
• 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)
• Project Period (FY): 2014-04-01 – 2018-03-31
• Keywords: 脳小血管病 / ショウジョウバエ / Notch

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.

Free Research Field

遺伝性神経疾患の研究