| Project/Area Number |
18K06478
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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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| Review Section |
Basic Section 46010:Neuroscience-general-related
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| Research Institution | The University of Tokyo |
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Principal Investigator |
Kassai Hidetoshi 東京大学, 大学院医学系研究科(医学部), 准教授 (40403232)
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| Project Period (FY) |
2018-04-01 – 2022-03-31
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| Project Status |
Completed (Fiscal Year 2021)
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| Budget Amount *help |
¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2020: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2019: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2018: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
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| Keywords | mTOR / Flightless-I / knockout mice / Flii / 遺伝子操作マウス / 行動解析 / 脳神経 |
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| Outline of Final Research Achievements |
In this study, I analyzed mTOR protein complex extracted from the mouse cerebral cortex by mass spectrometry, and identified the novel mTOR-interacting protein, Flightless-I (Flii). Flii is known as the cytoskeleton-regulating protein, but little is known about its function in the central nervous system.
We generated dorsal telencephalon-specific Flii conditional knockout mice (Flii cKO) by CRISPR/Cas9 system. The histological analysis revealed the atrophy of the cerebral cortex in Flii cKO mice, probably due to the apoptotic cell death of cortical progenitor cells during embryonic period. These phenotypes were also observed in the transgenic mice expressing active mTOR in the dorsal telencephalon. Therefore, Flii involved in the brain development, and may have relationship with the mTOR signaling.
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| Academic Significance and Societal Importance of the Research Achievements |
mTORシグナルは、がんや結節性硬化症、自閉症、神経編疾患など、ヒトの多様な疾患に深く関与していることが知られており、その発症メカニズムや治療法が深く研究されている分野である。本研究では大脳皮質における新規のmTOR 相互作用因子として同定されたFliiの機機能解析を遺伝子改変マウスを用いて行った。Fliiノックアウトマウスの表現型は、mTORシグナルが過剰に活性化したマウスと類似している。このことから、学術的にはこれまで十分明らかではなかった神経系におけるmTORシグナルの機能に迫ることができ、社会的にはヒトの疾患のメカニズムの解明や治療戦略に寄与できると考えられる。
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