Neuroepigenetic regulation of gene expression by DNA topooisomesase IIbeta
| Project/Area Number |
18K06349
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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 45010:Genetics-related
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| Research Institution | Okayama University |
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Principal Investigator |
Miyaji Mary 岡山大学, 医歯薬学総合研究科, 助教 (50349255)
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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: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2018: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
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| Keywords | Nerobiology / Epigenetics / Social behavior / Nuclear structure / 神経細胞 / 終末分化 / 核内構造 / 遺伝子発現制御 / 神経特異的遺伝子 / 神経細胞分化 / エピジェネティック / ニューロン |
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| Outline of Final Research Achievements |
We established three lines in which mutations were introduced into the topo IIβ gene by genome editing. The topo IIβ homozygous mutants were found to be lethal within a week after hatching. We performed mRNA-seq analyses using heads of homozygous, heterozygous, and wild-type individuals immediately after hatching, and revealed that the expression of many neuron-specific long genes was decreased in the homozygous mutants. Similar decreases were observed in the heterozygotes, though the decrease was lower in the heterozygotes than in the homozygotes. We are trying to discover behavioral abnormalities of heterozygous mutants with a focus on social behaviors.
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| Academic Significance and Societal Importance of the Research Achievements |
本研究では日本オリジナルのモデル脊椎動物であるメダカを用いて遺伝学と行動学的解析を組合せることにより，トポIIβが新規のエピジェネティック制御で神経機能に重要な遺伝子の発現を制御する機構と，その破綻が高次脳機能に及ぼす影響を明らかにすることを目的として行われた．実際，トポIIβが発現誘導する遺伝子が多数同定され，それらに多くの神経・精神疾患の関連遺伝子が含まれていた．今後の行動評価実験によりASDをはじめとする精神神経疾患の病態理解に繋がることが期待される
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Report
(4 results)
Research Products
(5 results)
