Pathophysiological mechanisms for microcephaly and macrocephaly
| Project/Area Number |
18K06504
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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 46020:Anatomy and histopathology of nervous system-related
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| Research Institution | Tokyo Medical and Dental University |
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Principal Investigator |
Hikaru Ito 東京医科歯科大学, 統合研究機構, 助教 (50587392)
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| Project Period (FY) |
2018-04-01 – 2021-03-31
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| Project Status |
Completed (Fiscal Year 2020)
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| Budget Amount *help |
¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2020: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2019: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2018: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
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| Keywords | 神経発達障害 / 小頭症 / 発生 / モデル動物 / 神経科学 / 発達障害 / 分化 |
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| Outline of Final Research Achievements |
There are no therapeutic methods for microcephaly and macrocephaly. Moreover, pathophysiological mechanisms underlying these neurodevelopmental disorders remain unclear. Therefore, we had tried to generate novel kdm5c mutant cell and mouse models by using CRISPR-Cas9 system for developing models of microcephaly and macrocephaly.
At first, we developed the cell models. And, we also analysed the gene expression levels in the cells and brains of Kdm5c mutant mice which has been showed microcephaly. As a results, we found that some genes of the neural differentiation category were up-regulated in the cells and brains of Kdm5c mutant mice. And also, we found novel KDM5c binding protein which has been thought as a regulator of neural differentiation.
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| Academic Significance and Societal Importance of the Research Achievements |
本課題の研究成果によって、小頭症を引き起こす新たなメカニズムの一端を解明できる可能性が示唆された。小頭症の病態メカニズムは未だ不明な点が多く、今後、さらに精査していくことにより、将来的な小頭症の治療へと応用することも十分可能であると考えている。さらには、本研究成果を発端として小頭症だけでなく大頭症など脳の大きさに異常をきたす神経発達障害の根本的な治療法開発へとつなげていく。
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Report
(4 results)
Research Products
(9 results)
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[Journal Article] Dopaminergic signaling in the nucleus accumbens modulates stress-coping strategies during inescapable stress.2020
Author(s)
Cui, W., Aida, T., Ito, H., Kobayashi, K., Wada, Y., Kato, S., Nakano, T., Zhu, M., Isa, K., Kobayashi, K., Isa, T., Tanaka, K. and Aizawa, H.
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Journal Title
J Neurosci.
Volume: 40
Issue: 38
Pages: 7241-7254
DOI
NAID
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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