| Project/Area Number |
16H05437
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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 |
Neurosurgery
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| Research Institution | Kyoto University |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
高橋 淳 京都大学, iPS細胞研究所, 教授 (10270779)
高木 康志 徳島大学, 大学院医歯薬学研究部(医学域), 教授 (40312227)
小泉 昭夫 京都大学, 医学研究科, 名誉教授 (50124574)
峰晴 陽平 京都大学, 医学研究科, 助教 (50716602)
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| Research Collaborator |
KATAOKA hiroharu
FUNAKI takashi
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| Project Period (FY) |
2016-04-01 – 2019-03-31
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| Project Status |
Completed (Fiscal Year 2018)
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| Budget Amount *help |
¥17,550,000 (Direct Cost: ¥13,500,000、Indirect Cost: ¥4,050,000)
Fiscal Year 2018: ¥5,330,000 (Direct Cost: ¥4,100,000、Indirect Cost: ¥1,230,000)
Fiscal Year 2017: ¥5,330,000 (Direct Cost: ¥4,100,000、Indirect Cost: ¥1,230,000)
Fiscal Year 2016: ¥6,890,000 (Direct Cost: ¥5,300,000、Indirect Cost: ¥1,590,000)
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| Keywords | 脳血管障害 / もやもや病 / RNF213 / 脳血管障害学 / 脳卒中 |
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| Outline of Final Research Achievements |
We aimed to identify genetic and epigenetic factors for moyamoya disease other than RNF213. We also tried to establish in vitro and in vivo models of moyamoya disease using iPS cells and R4810K knock-in mice. Whole genome sequencing in patients with moyamoya disease without the R4810K mutation identified several candidate genes, and whole genome methylation analysis of familial moyamoya disease with discordant phenotypes identified disease associated epigenetic changes. Both endothelial cells and vascular smooth muscle cells were differentiated from patient-derived iPS cells. These cells will be used to make an in vitro model of moyamoya disease for drug screening. We created both knock-out and knock-in (R4810K) mice, which will be used to develop an animal model of moyamoya disease.
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| Academic Significance and Societal Importance of the Research Achievements |
脳血管疾患は要介護の原因の約3割を占め、超高齢化社会を迎える我が国において重要な疾患である。脳血管疾患の半分は脳梗塞であり、動脈硬化によって生じるアテローム血栓性脳梗塞に関しては研究が進んでいるが、動脈硬化以外に原因でおこる脳血管狭窄については、分子メカニズムに不明な点が多く、新規治療開発の妨げとなってきた。本研究は我が国における代表的な非動脈硬化性脳血管狭窄であるもやもや病の感受性遺伝子として同定されたRNF213の生体内での役割を明らかにし、RNF213以外の遺伝因子や環境因子を解明する端緒となる研究で、同疾患の成因の解明や新規治療法の開発につながるものである。
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