Analysis of mice modified with genes controlling the amplitude of circadian rhythm by CRISPR / Cas9 method
Project/Area Number |
16K15193
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Research Category |
Grant-in-Aid for Challenging Exploratory Research
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Allocation Type | Multi-year Fund |
Research Field |
Environmental physiology(including physical medicine and nutritional physiology)
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Research Institution | Saitama Medical University |
Principal Investigator |
IKEDA MASAAKI 埼玉医科大学, 医学部, 教授 (80232198)
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Research Collaborator |
KUMAGAI megumi
NAKAJIMA yoshihiro
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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 |
¥3,510,000 (Direct Cost: ¥2,700,000、Indirect Cost: ¥810,000)
Fiscal Year 2017: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2016: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
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Keywords | 時計遺伝子 / 概日リズム / Bmal1 / 視交叉上核 / ゲノム編集 / うつ病 / うつ病モデル / CRISPR/Cas9 / 遺伝子ノックダウン / 振幅 / 周期 / 気分障害 / リズム振幅 |
Outline of Final Research Achievements |
Postmortem brain studies reported that the circadian rhythmic expression of clock genes was attenuated in the dorsolateral prefrontal cortex and anterior cingulate cortex (Li et al, PNAS 2013). This report suggested that depression has circadian rhythm dysfunction in the brain. The goal of this study was to create a depression model mouse with reduced amplitude of circadian rhythm in the brain region associated with the cause of depression. As a preparatory step for creating a model mouse, knockout cells of SRC1 of the p160 family, a factor that enhances the amplitude of the circadian rhythm, were created. The SRC1 knockout cells were shown to reduce the amplitude of Bmal1 and Per2 promoter rhythms.
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Academic Significance and Societal Importance of the Research Achievements |
概日リズムの機能が中枢神経系で減弱することは、感情障害の発症要因となることが想定されている。私たちは概日リズムの振幅を制御する因子を探索している。その過程でp160因子が振幅の増強に関わっていることを発見した。今回、この因子の発現を増強あるいは低下させたモデル細胞を作出し、概日リズム振幅の増減が細胞機能に及ぼす影響を解析した。今後はp160の機能を改変し、時計遺伝子発現リズムの振幅をうつ病発症と関連するとされる領域の神経細胞で減弱化させたマウスを作出し、中枢神経系におけるリズム振幅減弱化と感情障害との関連を解析する計画であり、これらの成果はうつ病の解明や新しい治療法開発につながると考えている。
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Report
(4 results)
Research Products
(14 results)
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[Journal Article] Cell-based screen identifies a new potent and highly selective CK2 inhibitor for modulation of circadian rhythms and cancer cell growth.2019
Author(s)
Oshima T, Niwa Y, Kuwata K, Srivastava A, Hyoda T, Tsuchiya Y, Kumagai M, Tsuyuguchi M, Tamaru T, Sugiyama A, Ono N, Zolboot N, Aikawa Y, Oishi S, Nonami A, Arai F, Hagihara S, Yamaguchi J, Tama F, Kunisaki Y, Yagita K, Ikeda M, Kinoshita T, Kay SA, Itami K, Hirota T.
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Journal Title
Science Advance
Volume: 23
Issue: 1
Pages: 9060-9060
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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