Genetic analysis of central nervous system by using conditional mutant mice

• Project/Area Number: 17024038
• Research Category: Grant-in-Aid for Scientific Research on Priority Areas
• Allocation Type: Single-year Grants
• Review Section: Biological Sciences
• Research Institution: Kobe University
• Principal Investigator: AIBA Atsu Kobe University, 大学院・医学系研究科, 教授 (20271116)
• Project Period (FY): 2005 – 2009
• Project Status: Completed (Fiscal Year 2009)
• Budget Amount: ¥105,800,000 (Direct Cost: ¥105,800,000); Fiscal Year 2009: ¥21,500,000 (Direct Cost: ¥21,500,000); Fiscal Year 2008: ¥20,600,000 (Direct Cost: ¥20,600,000); Fiscal Year 2007: ¥19,800,000 (Direct Cost: ¥19,800,000); Fiscal Year 2006: ¥20,900,000 (Direct Cost: ¥20,900,000); Fiscal Year 2005: ¥23,000,000 (Direct Cost: ¥23,000,000)
• Keywords: mGluR1 / Rac / トランスジェニックマウス / ノックアウトマウス / プルキンエ細胞 / テトラサイクリン / 瞬目反射条件付け / テトラサイクリン誘導システム / ERK / プルキンエ細胞特異 / Rac1 / 脳梁 / 質量分析 / MEK

Research Abstract

We established the mGluR1 cKO mice in which mGluR1 expression can be turned off with doxycycline. Using mGluR1 cKO mice, we showed that mGluR1 is essential for motor coordination in adulthood and that conditioned eyeblink memory was not formed without mGluR1 but once formed memory was maintained and expressed without mGluR1.
We also showed that a Rho family GTPase Rac1 specifically controls the midline crossing of the commissural axons during cortical development, rather than neuronal migration and axonal formation.

Research Products

• [Journal Article] Development of the somatosensory cortex, the cerebellum, and the main olfactory system in semaphorin 3F knockout mice. (2010)
  • Author(s): Matsuda, I., Fukaya, M., Nakao, H., Nakao, K., Matsumoto, H., Mori, K., Watanabe, M., Aiba, A.
  • Journal Title: Neurosci. Res. 66 Pages: 321-329
  • NAID: 10027501273
  • Peer Reviewed
• [Journal Article] Development of the somatosensory cortex, the cerebellum, and the main olfactory system in semaphorin 3F knockout mice (2010)
  • Author(s): Matsuda, et al.
  • Journal Title: Neurosci.Res. 66 Pages: 321-329
  • NAID: 10027501273
  • Peer Reviewed
• [Journal Article] Crucial role of the small GTPase Racl in insulin-stimulated translocation of glucose transporter 4 to the mouse skeletal muscle sarcolemma (2010)
  • Author(s): Ueda, et al.
  • Journal Title: FASEB J. (掲載確定)
  • Peer Reviewed
• [Journal Article] Requirement of the immediate early gene vesl-1S/homer-1a for fear memory formation. (2009)
  • Author(s): Inoue, N., Nakao, H., Migishima, R., Hino, T., Matsui, M., Hayashi, F., Nakao, K., Manabe, T., Aiba, A., Inokuchi, K.
  • Journal Title: Mol. Brain 2 Pages: 7-7
  • Peer Reviewed
• [Journal Article] Odor-induced persistent discharge of mitral cells in mouse olfactory bulb. (2009)
  • Author(s): Matsumoto, H., Kashiwadani, H., Nagao, H., Aiba, A., Mori, K.
  • Journal Title: J. Neurophysiol 101 Pages: 1890-1900
  • Peer Reviewed
• [Journal Article] Essential mesenchymal role of small GTPase Racl in inter-digital programmed cell death during limb development (2009)
  • Author(s): Suzuki, et al.
  • Journal Title: Dev.Biol. 335 Pages: 396-406
  • Peer Reviewed
• [Journal Article] Dorsal telencephalon-specific RA-GEF-1 knockout mice develop heterotopic cortical mass and commissural fiber defect (2009)
  • Author(s): Bilasy, et al.
  • Journal Title: Eur.J.Neurosci. 29 Pages: 1994-2008
  • Peer Reviewed
• [Journal Article] Requirement of the immediate early gene vesl-1S/homer-1a for fear memory formation (2009)
  • Author(s): Inoue, et al.
  • Journal Title: Mol.Brain 2
  • Peer Reviewed
• [Journal Article] Odor-induced persistent discharge of mitral cells in the mouse olfactory bulb (2009)
  • Author(s): Matsumoto, et al.
  • Journal Title: J.Neurophysiol. 101 Pages: 1890-1900
  • Peer Reviewed
• [Journal Article] Metabotropic glutamate receptor subtype-1 is essential for in vivo growth of melanoma. (2008)
  • Author(s): Ohtani, Y., Harada, T., Funasaka, Y., Nakao, K., Takahara, C., Abdel-Daim, M., Sakai, N., Saito, N., Nishigori, C., Aiba, A.
  • Journal Title: Oncogene 27 Pages: 7162-7170
  • Peer Reviewed
• [Journal Article] Rac1 in cortical projection neurons is selectively required for midline crossing of commissural axonal formation. (2008)
  • Author(s): Kassai, H., Terashima, T., Fukaya, M., Nakao, K., Sakahara, M., Watanabe, M., Aiba, A.
  • Journal Title: Eur. J. Neurosci 28 Pages: 257-267
  • Peer Reviewed
• [Journal Article] Semaphorin 3F confines ventral tangential migration of lateral olfactory tract neurons onto the telencephalon surface. (2008)
  • Author(s): Ito, K., Kawasaki, T., Takashima, S., Matsuda, I., Aiba, A., Hirata, T.
  • Journal Title: J. Neurosci 28 Pages: 4414-4422
  • Peer Reviewed
• [Journal Article] FSP27 contributes to efficient energy storage in murine white adipocytes by promoting the formation of unilocular lipid droplets (2008)
  • Author(s): Nishino, et.al.
  • Journal Title: J. Clin Invest 118 Pages: 2808-2821
  • Peer Reviewed
• [Journal Article] Racl in cortical projection neurons is selectively required for midline crossing of commissural axonal formation (2008)
  • Author(s): Kassai, et.al.
  • Journal Title: Eur. J. Neurosci 28 Pages: 257-267
  • Peer Reviewed
• [Journal Article] Metabotropic glutamate receptor subtype-1 is essential for in vivo growth of melanoma (2008)
  • Author(s): Ohtani, et.al.
  • Journal Title: Oncogene 27 Pages: 7162-7170
  • Peer Reviewed
• [Journal Article] Semaphorin 3F confines ventral tangential migration of lateral olfactory tract onto telencephalon surface. (2008)
  • Author(s): Ito, et. al.
  • Journal Title: J. Neurosci. (印刷中)
  • Peer Reviewed
• [Journal Article] G protein-independent neuromodulatory action of adenosine on metabotropic glutamate signaling in mouse cerebellar Purkinje Cells. (2007)
  • Author(s): Tabata, T., Kawakami, D., Hashimoto, K., Kassai, H., Yoshida, T., Hashimotodani, Y., Fredholm, B., B., Seikno, Y., Aiba, A., Kano, M.
  • Journal Title: J. Physiol 581 Pages: 693-708
  • Peer Reviewed
• [Journal Article] Conditional mutant mice using tetracycline-controlled gene expression system in the brain. (2007)
  • Author(s): Aiba, A., Nakao, H.
  • Journal Title: Neurosci Res 58 Pages: 113-117
  • NAID: 10024414832
  • Peer Reviewed
• [Journal Article] Mouse liaison for integrative brain research. (2007)
  • Author(s): Aiba, A., Inokuchi, K., Ishida, Y., Itohara, S., Kobayashi, K., Masu, M., Mishina, M., Miyakawa, T., Mori, H., Nakao, K., Obata, Y., Sakimura, K., Shiroishi, T., Wada, K., Yagi, T.
  • Journal Title: Neurosci Res 58 Pages: 103-104
  • NAID: 10024414758
  • Peer Reviewed
• [Journal Article] Metabotropic glutamate receptor subtype-1 is essential for motor coordination in the adult cerebellum. (2007)
  • Author(s): Nakao, H., Nakao, K., Kano, M., Aiba, A.
  • Journal Title: Neurosci. Res. 57 Pages: 538-543
  • NAID: 10024413956
  • Peer Reviewed
• [Journal Article] The M-Ras-RA-GEF-2-Rapl pathway mediates tumor necrosis factor-α-dependent regulation ofintegrin activation in splenocytes. (2007)
  • Author(s): Yoshikawa, et. al.
  • Journal Title: Mol. Biol. Cell 18 Pages: 2949-2959
  • Peer Reviewed
• [Journal Article] Defective vascular morphogenesis and mid-gestation embryonic death in mice lacking RA-GEF-1. (2007)
  • Author(s): Wei, et. al.
  • Journal Title: Biochem. Biophys. Res. Commun. 363 Pages: 106-112
  • Peer Reviewed
• [Journal Article] Conditional mutant mice using tetracycline-controlled gene expression system in the brain. (2007)
  • Author(s): Aiba, Nakao
  • Journal Title: Neurosci. Res. 58 Pages: 113-117
  • NAID: 10024414832
  • Peer Reviewed
• [Journal Article] Metabotropic glutamate receptor subtype-1 is essential for motor coordination in the adult cerebellum. (2007)
  • Author(s): Nakao et al.
  • Journal Title: Neurosci. Res. 57・4 Pages: 538-543
• [Journal Article] Farnesylation of retinal transducin underlies its translocation during light adaptation. (2005)
  • Author(s): Kassai, H., Aiba, A., Nakao, K., Nakamura, K., Katsuki, M., Xiong, WH., Yau, KW., Imai, H., Shichida, Y., Satomi, Y., Takao, T., Okano, T., Fukada, Y.
  • Journal Title: Neuron 47 Pages: 529-539
  • Peer Reviewed
• [Journal Article] Synaptically driven endocannabinoid release requires Ca2+-assisted metabotropic glutamate receptor subtype 1 to phospholipase Cbeta4 signaling cascade in the cerebellum. (2005)
  • Author(s): Maejima, T., Oka, S., Hashimotodani, Y., Ohno-Shosaku, T., Aiba, A., Wu, D., Waku, K., Sugiura, T., Kano, M.
  • Journal Title: J. Neurosci 25 Pages: 6826-6835
  • Peer Reviewed
• [Journal Article] Farnesylation of retinal transducin underlies its translocation during light adaptation. (2005)
  • Author(s): Kassai et al.
  • Journal Title: Neuron 47・4 Pages: 529-539
• [Journal Article] Synaptically driven endocannabinoid release requires Ca2+-assisted metabotropic glutamate receptor subtype 1 to phospholipase Cbeta4 signaling cascade in the cerebellum. (2005)
  • Author(s): Maejima et al.
  • Journal Title: J.Neurosci. 25・29 Pages: 6826-6835
• [Journal Article] G protein-independent neuromodulatory action of adenosine on metabotropic glutamate signaling in mouse cerebellar Purkinje cells.
  • Author(s): Tabata et al.
  • Journal Title: J. Physiol. (印刷中)
• [Presentation] 小脳プルキンエ細胞におけるmGluR1-Homer 複合体の生理機能解析 (2009)
  • Author(s): 葛西秀俊
  • Organizer: 第32回日本分子生物学会年会
  • Place of Presentation: パシフィコ横浜
  • Year and Date: 2009-12-10
• [Presentation] mGluR1は瞬目反射条件付け記憶の獲得に必要であり (2009)
  • Author(s): 中尾晴美, 岸本泰司, 橋本浩一, 中尾和貴, 狩野方伸, 桐野豊, 饗場篤
  • Organizer: その発現や保持には必要でない第32回日本神経科学大会
  • Place of Presentation: 名古屋
  • Year and Date: 2009-09-17
• [Presentation] mGluR1は瞬目反射条件付け記憶の獲得に必要であり、その発現や保持には必要でない (2009)
  • Author(s): 中尾晴美
  • Organizer: 第32回 日本神経科学大会
  • Place of Presentation: 名古屋国際会議場
  • Year and Date: 2009-09-17
• [Presentation] mGluR1は悪性黒色腫の増殖に必要である (2008)
  • Author(s): 原田武志, 大谷善昭, 船坂陽子, 中尾和貴, 高原千明, M Abdel-Daim, 酒井規雄, 齋藤尚亮, 錦織千佳子, 饗場篤
  • Organizer: 第31回日本分子生物学会年会・第81回日本生化学会大会合同大会
  • Place of Presentation: 神戸
  • Year and Date: 2008-12-09
• [Presentation] ERKは発達期小脳におけるシナプスの除去に必要である (2008)
  • Author(s): 原田武志, 平井良枝, 山崎美和子, 橋本浩一, 中尾晴美, 田端俊英, 中尾和貴, 渡辺雅彦, 狩野方伸, 饗場篤
  • Organizer: 第31回日本神経科学大会
  • Place of Presentation: 東京
  • Year and Date: 2008-07-10
• [Presentation] Small G protein Rac1 is selectively required for the formation of commissural axons in the cerebral cortex (2008)
  • Author(s): Hidetoshi Kassai, Toshio Terashima, Masahiro Fukaya, Kazuki Nakao, Mizuho Sakahara, Masahiko Watanabe, Atsu Aiba
  • Organizer: 38th annual meeting of the Society for Neuroscience
  • Place of Presentation: Washington DC, USA
• [Presentation] Small G protein Racl is selectively required for the formation of commissural axons in the cerebral cortex (2008)
  • Author(s): Kassai, et.al.
  • Organizer: 37th annual meeting of the Society for Neuroscience
  • Place of Presentation: Washington DC, USA
• [Presentation] mGluR1シグナルの遺伝学的解析及びプロテオミクス解析 (2007)
  • Author(s): 饗場篤
  • Organizer: 第30回日本神経科学大会・第50回日本神経化学会大会・第17回日本神経回路学会大会合同大会
  • Place of Presentation: 横浜
  • Year and Date: 2007-09-12
• [Presentation] mGluR1シグナルの遺伝学的解析及びプロテオミクス解析 (2007)
  • Author(s): 〓場 篤
  • Organizer: 第30回日本神経科学大会
  • Place of Presentation: 横浜
  • Year and Date: 2007-09-12
• [Presentation] ERKは恐怖記憶の形成に必要である (2007)
  • Author(s): 原田武志, 城山優治, 中尾和貴, 真鍋俊也, 饗場篤
  • Organizer: 第30回日本神経科学大会・第50回日本神経化学会大会・第17回日本神経回路学会大会合同大会
  • Place of Presentation: 横浜
  • Year and Date: 2007-09-10
• [Presentation] mGluR1 is essential for motor coordination in the adult cerebellum. (2007)
  • Author(s): Aiba, A., Nakao, H., Nakao, K., Kano, M.
  • Organizer: 37th Annual meeting of the Society for Neuroscience
  • Place of Presentation: San Diego, USA
• [Presentation] mGluR1の複合体分析による小脳機能の解析 (2007)
  • Author(s): 葛西秀俊, 早野俊哉, 高橋信弘, 饗場篤
  • Organizer: 日本ヒトプロテオーム機構第5回大会
  • Place of Presentation: 東京
• [Presentation] A comprehensive behavioral test battery reveals novel physiological roles of Semaphorin 3F in postnatal brain functions. (2006)
  • Author(s): Ikuo Matsuda, Nobuyuki Yamasaki, Sei-ichi Hirota, Tsuyoshi Miyakawa, Atsu Aiba
  • Organizer: 第20回国際生化学・分子生物学会議/第11回アジア・オセアニア生化学者・分子生物学者連合会議, 第79回日本生化学会大会, 第29回日本分子生物学会年会
  • Place of Presentation: 京都
  • Year and Date: 2006-06-20
• [Presentation] C-terminal domain of mGluR1a is essential for synapse elimination and eye-blink conditioning. (2005)
  • Author(s): Yoshiaki Ohtani, Kouichi Hashimoto, Hidetoshi Tabata, Yasushi Kishimoto, Masahiro Fukaya, Kazuki Nakao, Hidetoshi Kassai, Masahiko Watanabe, Masanobu Kano, Atsu Aiba
  • Organizer: 第28回日本神経科学会大会
  • Place of Presentation: 横浜
• [Presentation] 代謝型グルタミン酸受容体と高次脳機能 (2005)
  • Author(s): 饗場篤
  • Organizer: 第28回日本神経科学会大会
  • Place of Presentation: 横浜
• [Remarks]
  • URL: http://lar.cdbim.m.u-tokyo.ac.jp/index.html
• [Remarks]
  • URL: http://lar.cdbim.m.u-tokyo.ac.jp/index.html