Fine visualization of oxytocin receptor expressing neurons via the novel labeling system
Project/Area Number |
20K06467
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Research Category |
Grant-in-Aid for Scientific Research (C)
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Allocation Type | Multi-year Fund |
Section | 一般 |
Review Section |
Basic Section 42040:Laboratory animal science-related
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Research Institution | National Center of Neurology and Psychiatry |
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, リサーチフェロー (30611777)
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Project Period (FY) |
2020-04-01 – 2023-03-31
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Project Status |
Completed (Fiscal Year 2022)
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Budget Amount *help |
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2022: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2021: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2020: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
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Keywords | オキシトシン受容体 / ゲノム編集 / ノックインマウス |
Outline of Research at the Start |
脳内の神経伝達物質として働くオキシトシンは、その受容体を発現する神経細胞の機能を修飾し、養育行動・夫婦や家族の絆・他者への信頼などの「社会性行動」を促進的に制御する。オキシトシン系神経回路の入出力は極めて複雑であり、既存の遺伝子改変マウスを用いて、オキシトシン受容体が神経細胞のどの部分にあるのかを区別することはできず、神経回路を詳細に解析するには不十分である。本研究では、ゲノム編集技術を駆使して新たな神経細胞可視化システムを構築し、社会性行動を制御するオキシトシン系神経回路網の「可視化」と「操作」を加速するツールを提供する。
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Outline of Final Research Achievements |
Oxytocin, which acts as a neurotransmitter in the brain, has attracted widespread interest because it modulates the function of neurons that express its receptor to facilitatively regulate social behaviors such as nursing behavior and family bonding. Hence, research to better understand the oxytocin neural network is very active now. However, existing antibodies and mouse models are insufficient to accurately visualize the expression of this receptor. In this study, we newly generated multiple knock-in mouse lines by genome editing using fertilized eggs, to detect the sub-cellular localization of oxytocin receptors with unprecedented precision. In addition, we provided domestic and foreign researchers with mouse tools expressing fluorescent reporters and Cre recombinase, which are essential for manipulating oxytocin neural circuits in the brain. By developing these resources, we have contributed to the promotion of oxytocin research on a worldwide level.
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Academic Significance and Societal Importance of the Research Achievements |
オキシトシン受容体は高脂溶性の膜タンパク質のため、これを認識する抗体を作製することは難しく、マウス脳組織上で研究に使用できる良好な抗体が存在しなかった。そこで、受容体タンパク質の末端にタグを付加したノックインマウスをゲノム編集により作出し、タグに対する抗体を用いて超解像度顕微鏡解析を行い、受容体の神経細胞内局在を初めて観察することができた。また、オキシトシン神経回路の操作による機能解析に必須の蛍光レポーターやCre組換え酵素発現マウスも作出し、国際的なバイオリソースに寄託することにより、国内外のオキシトシン研究者への提供を容易にし、社会性行動を制御する神経回路網の理解を深めることに貢献した。
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Report
(4 results)
Research Products
(60 results)
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[Journal Article] Myopathy associated with dermatan sulfate-deficient decorin and myostatin in musculocontractural Ehlers-Danlos syndrome: a mouse model investigation2021
Author(s)
Yuko Nitahara-Kasahara, Guillermo Posadas-Herrera, Shuji Mizumoto, Aki Nakamura-Takahashi, Yukiko U. Inoue, Takayoshi Inoue, Yoshihiro Nomura, Shin’ichi Takeda, Shuhei Yamada, Tomoki Kosho, Takashi Okada
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Journal Title
Frontiers in Cell and Developmental Biology
Volume: 9
Pages: 695021-695021
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] Down syndrome cell adhesion molecule like-1 (DSCAML1) links the GABA system and seizure susceptibility.2020
Author(s)
Hayase Y, Amano S, Hashizume K, Tominaga T, Miyamoto H, Kanno Y, Ueno-Inoue Y, Inoue T, Yamada M, Ogata S, Balan S, Hayashi K, Miura Y, Tokudome K, Ohno Y, Nishijo T, Momiyama T, Yanagawa Y, Takizawa A, Mashimo T, Serikawa T, Sekine A, Nakagawa E, Takeshita E, Yoshikawa T, Waga C, Inoue K, Goto YI, Nabeshima Y, et al.
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Journal Title
Acta Neuropathol Commun.
Volume: 8
Issue: 1
Pages: 206-206
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] DSCAM regulates delamination of neurons in the developing midbrain2020
Author(s)
Arimura Nariko、Okada Mako、Taya Shinichiro、Dewa Ken-ichi、Tsuzuki Akiko、Uetake Hirotomo、Miyashita Satoshi、Hashizume Koichi、Shimaoka Kazumi、Egusa Saki、Nishioka Tomoki、Yanagawa Yuchio、Yamakawa Kazuhiro、Inoue Yukiko U.、Inoue Takayoshi、Kaibuchi Kozo、Hoshino Mikio
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Journal Title
Science Advances
Volume: 6
Issue: 36
Pages: 1693-1693
DOI
Related Report
Peer Reviewed / Open Access
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[Presentation] ARRHYTHMIA SEVERITY IN MOUSE MODELS HARBORING RYR2 MUTATIONS WITH VARIED EXTENT OF CHANNEL ACTIVITY2023
Author(s)
Nagomi Kurebayashi, Masami Kodama, Takashi Murayama, Masami Sugihara, Masato Konishi, Aya Miura, Hajime Nishio, Yukiko U. Inoue, Takayoshi Inoue, Satoru Noguchi, Takashi Sakurai
Organizer
67th Biophysical Society Annual Meeting
Related Report
Int'l Joint Research
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[Presentation] Targeting neurons with functional oxytocin receptors: A novel set of simple knock-in mouse lines for oxytocin receptor visualization and manipulation2022
Author(s)
Yukiko U. Inoue, Hideki Miwa, Kei Hori, Ryosuke Kaneko, Yuki Morimoto, Eriko Koike, Junko Asami, Satoshi Kamijo, Mitsuhiko Yamada, Mikio Hoshino, Takayoshi Inoue
Organizer
Society for Neuroscience 51st Annual Meeting
Related Report
Int'l Joint Research
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