Brain region-specific enhancer activities for oxytocin receptor gene: the relationship with autism-associated SNPs
| Project/Area Number |
16K10004
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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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| Research Field |
Pediatrics
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| Research Institution | National Center of Neurology and Psychiatry |
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Principal Investigator |
Inoue U. Yukiko 国立研究開発法人国立精神・神経医療研究センター, 神経研究所 疾病研究第六部, 科研費研究員 (30611777)
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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 |
¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000)
Fiscal Year 2018: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2017: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Fiscal Year 2016: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
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| Keywords | オキシトシン受容体 / 自閉スペクトラム症 / SNP / ゲノム編集 / CRISPR/Cas9 / エンハンサー / BAC / ヒトBAC / CRISPR/Cas9ゲノム編集 / 自閉症スペクトラム関連SNP |
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| Outline of Final Research Achievements |
Autism-associated polymorphisms (SNPs) within the intronic sequences of oxytocin receptor (OXTR) gene have been continually reported to correlate with variations in social behaviors. However, how the intronic "non-coding" sequence variations can affect OXTR expression patterns, neuronal connections, and the behavioral phenotypes remains elusive. In this study, we employed the latest genome editing technology to generate novel knock-in reporter mouse lines by which we could precisely recapitulate the brain region-specific OXTR expression profiles. We also utilized these mouse models to investigate brain enhancer activities for OXTR expressions within the intronic sequences. These new tools could be widely shared in science community to investigate roles of oxytocin-oxytocin receptor system in social brains.
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| Academic Significance and Societal Importance of the Research Achievements |
オキシトシンは、オキシトシン受容体を持つ神経細胞の機能を修飾することにより、家族や夫婦の絆・仲間同士の信頼などの「社会性行動」を促進する。オキシトシン受容体遺伝子のイントロン（受容体蛋白質をコードする情報を持っていない部分）には、自閉スペクトラム症などの社会性行動の多様性と相関するような塩基配列のバリエーションが多数見出されているが、その役割はわかっていない。本研究では、マウス受精卵を用いた最新のゲノム編集法を駆使して、そのイントロン配列にオキシトシン受容体の発現調節機能があるかどうかを調べることができるマウスモデルを作製した。今後のオキシトシン系神経回路の研究において有用なツールとなりうる。
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Report
(4 results)
Research Products
(27 results)
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[Journal Article] Origins of oligodendrocytes in the cerebellum, whose development is controlled by the transcription factor, Sox92016
Author(s)
Hashimoto R, Hori K, Owa T, Miyashita S, Dewa K, Masuyama N, Sakai K, Hayase Y, Seto Y, Inoue YU, Inoue T, Ichinohe N, Kawaguchi Y, Akiyama H, Koizumi S, Hoshino M
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Journal Title
Mech Dev
Volume: 140
Pages: 25-40
DOI
Related Report
Peer Reviewed / Acknowledgement Compliant
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