Study of GABAergic transmission mechanism using glutamate decarboxylase knockout mice

• Project/Area Number: 26290002
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Partial Multi-year Fund
• Section: 一般
• Research Field: Neurophysiology / General neuroscience
• Research Institution: Gunma University
• Principal Investigator: YANAGAWA YUCHIO 群馬大学, 大学院医学系研究科, 教授 (90202366)
• Co-Investigator(Renkei-kenkyūsha): KAKIZAKI TOSHIKAZU 群馬大学, 大学院医学系研究科, 助教 (50375531) ; MIWA HIDEKI 群馬大学, 大学院医学系研究科, 助教 (80468488)
• Project Period (FY): 2014-04-01 – 2018-03-31
• Project Status: Completed (Fiscal Year 2017)
• Budget Amount: ¥16,900,000 (Direct Cost: ¥13,000,000、Indirect Cost: ¥3,900,000); Fiscal Year 2016: ¥4,030,000 (Direct Cost: ¥3,100,000、Indirect Cost: ¥930,000); Fiscal Year 2015: ¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000); Fiscal Year 2014: ¥8,060,000 (Direct Cost: ¥6,200,000、Indirect Cost: ¥1,860,000)
• Keywords: GABA / GAD65 / GAD67 / ノックアウトマウス / テトラサイクリン発現システム / 神経科学 / 脳・神経 / 酵素 / 脳神経疾患

Outline of Final Research Achievements

GABA is a major inhibitory neurotransmitter, and it is synthesized from glutamate by glutamate decarboxylase (GAD). There are two isoforms of GAD, GAD65 and GAD67. GAD67 knockout mice died at postnatal day 0 (P0), and thus they cannot be characterized after P0. We generated time-dependent GAD67 knockout mice. In addition, we generated GAD67 knockout rats, which were found alive after 3 weeks of age. These genetically engineered rodents will be a useful tool for clarifying the role of GAD67 and GABA in brain function.

Research Products

• [Int'l Joint Research] Otto-von-Guericke University Magdeburg(ドイツ)
• [Int'l Joint Research] Otto-von-Guericke University Magdeburg(ドイツ)
• [Int'l Joint Research] The University of Queensland(オーストラリア)
• [Int'l Joint Research] Pierre and Marie Curie University(フランス)
• [Journal Article] Distinct response properties of rat prepositus hypoglossi nucleus neurons classified on the basis of firing patterns. (2017)
  • Author(s): Saito Y, Yanagawa Y
  • Journal Title: Neuroscience Research Volume: 印刷中 Pages: 18-28
  • DOI: 10.1016/j.neures.2017.03.003
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Abnormal gamma-aminobutyric acid neurotransmission in a Kcnq2 model of early onset epilepsy. (2017)
  • Author(s): Uchida T, Lossin C, Ihara Y, Deshimaru M, Yanagawa Y, Koyama S, Hirose S.
  • Journal Title: Epilepsia. Volume: 58(8) Issue: 8 Pages: 1430-9
  • DOI: 10.1111/epi.13807
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] A glycine transporter 2-Cre knock-in mouse line for glycinergic neuron-specific gene manipulation. (2017)
  • Author(s): Kakizaki T, Sakagami H, Sakimura K, Yanagawa Y.
  • Journal Title: IBRO Reports Volume: 3 Pages: 9-16
  • DOI: 10.1016/j.ibror.2017.07.002
  • Peer Reviewed / Open Access
• [Journal Article] Comparisons of neuronal and excitatory network properties between the rat brainstem nuclei that participate in vertical and horizontal gaze holding. (2017)
  • Author(s): Saito Y, Sugimura T, Yanagawa Y.
  • Journal Title: eNeuro Volume: 4(5) Issue: 5 Pages: ENEURO.0180-17.2017
  • DOI: 10.1523/eneuro.0180-17.2017
  • Peer Reviewed / Open Access
• [Journal Article] Inhibitory neuron-specific Cre-dependent red fluorescent labeling using VGAT BAC-based transgenic mouse lines with identified transgene integration sites (2017)
  • Author(s): Kaneko Ryosuke、Takatsuru Yusuke、Morita Ayako、Amano Izuki、Haijima Asahi、Imayoshi Itaru、Tamamaki Nobuaki、Koibuchi Noriyuki、Watanabe Masahiko、Yanagawa Yuchio
  • Journal Title: Journal of Comparative Neurology Volume: 526 Issue: 3 Pages: 373-396
  • DOI: 10.1002/cne.24343
  • Peer Reviewed
• [Journal Article] Medullary Reticular Neurons Mediate Neuropeptide Y-Induced Metabolic Inhibition and Mastication. (2017)
  • Author(s): Nakamura Y, Yanagawa Y, Morrison SF, Nakamura K.
  • Journal Title: Cell Metab. Volume: 25 Issue: 2 Pages: 322-334
  • DOI: 10.1016/j.cmet.2016.12.002
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Distinct development of the glycinergic terminals in the ventral and dorsal horns of the mouse cervical spinal cord. (2017)
  • Author(s): Sunagawa M, Shimizu-Okabe C, Kim J, Kobayashi S, Kosaka Y, Yanagawa Y, Matsushita M, Okabe A, Takayama C.
  • Journal Title: Neuroscience Volume: 343 Pages: 459-471
  • DOI: 10.1016/j.neuroscience.2016.12.032
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Alterations in hypoglossal motor neurons due to GAD67 and VGAT deficiency in mice. (2017)
  • Author(s): Fogarty MJ, Kanjhan R, Yanagawa Y, Noakes PG, Bellingham MC.
  • Journal Title: Exp Neurol. Volume: 289 Pages: 117-127
  • DOI: 10.1016/j.expneurol.2016.12.004
  • Peer Reviewed / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Monoaminergic modulation of GABAergic transmission onto cerebellar globular cells. (2017)
  • Author(s): Hirono M, Nagao S, Yanagawa Y, Konishi S.
  • Journal Title: Neuropharmacology Volume: 11 Pages: 79-89
  • DOI: 10.1016/j.neuropharm.2017.03.011
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Nicotinic acetylcholine receptor-mediated responses in medial vestibular and prepositus hypoglossi nuclei neurons showing distinct neurotransmitter phenotypes. (2016)
  • Author(s): Zhang, Y.;Yanagawa, Y.;Saito, Y.
  • Journal Title: J Neurophysiol, Volume: － Issue: 5 Pages: 2649-2657
  • DOI: 10.1152/jn.00852.2015
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Unique pH dynamics in GABAergic synaptic vesicles illuminates the mechanism and kinetics of GABA loading. (2016)
  • Author(s): Egashira Y, Takase M, Watanabe S, Ishida J, Fukamizu A, Kaneko R, Yanagawa Y, Takamori S.
  • Journal Title: Proc Natl Acad Sci USA Volume: 113 Issue: 38 Pages: 10702-10707
  • DOI: 10.1073/pnas.1604527113
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Diversity and overlap of Parvalbumin and Somatostatin expressing interneurons in mouse presubiculum. (2015)
  • Author(s): Nassar M, Simonnet J, Lofredi R, Cohen I, Savary E, Yanagawa Y, Miles R, Fricker D.
  • Journal Title: Front Neural Circuits Volume: 9 Pages: 20-20
  • DOI: 10.3389/fncir.2015.00020
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Glutamate Decarboxylase 67 Deficiency in a Subset of GABAergic Neurons Induces Schizophrenia-Related Phenotypes. (2015)
  • Author(s): Fujihara K, Miwa H, Kakizaki T, Kaneko R, Mikuni M, Tanahira C, Tamamaki N, Yanagawa Y
  • Journal Title: Neuropsychopharmacology. Volume: 40 Issue: 10 Pages: 2475-2486
  • DOI: 10.1038/npp.2015.117
  • Peer Reviewed
• [Journal Article] Nkx2.1-derived astrocytes and neurons are indispensable for the anterior commissure formation: a role for Slit2. (2015)
  • Author(s): Minocha S, Valloton D, Yspilanti AR, Fiumelli H, Allen EA, Yanagawa Y, Marin O, Chédotal A, Hornung JP, Lebrand C.
  • Journal Title: Nat Commun. Volume: 6 Issue: 1 Pages: 6887-6887
  • DOI: 10.1038/ncomms7887
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Corticofugal GABAergic projection neurons in the mouse frontal cortex. (2015)
  • Author(s): Tomioka R, Sakimura K, Yanagawa Y.
  • Journal Title: Front Neuroanat. Volume: 9 Pages: 133-133
  • DOI: 10.3389/fnana.2015.00133
  • Peer Reviewed / Open Access
• [Journal Article] GAD65/GAD67 double knockout mice exhibit intermediate severity in both cleft palate and omphalocele compared with GAD67 knockout and VGAT knockout mice (2015)
  • Author(s): Kakizaki T, Oriuchi N, Yanagawa Y
  • Journal Title: Neuroscience Volume: 288 Pages: 86-93
  • DOI: 10.1016/j.neuroscience.2014.12.030
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Functional alpha7 nicotinicreceptors are expressed on immature granule cells of the postnatal dentate gyrus (2015)
  • Author(s): John D, Shelukhina I, Yanagawa Y et al.
  • Journal Title: Brain Res. Volume: 1601 Pages: 15-30
  • DOI: 10.1016/j.brainres.2014.12.041
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Contribution of parvalbumin and somatostatin-expressing GABAergic neurons to slow oscillations and the balance in beta-gamma oscillations across cortical layers. (2015)
  • Author(s): Kuki T, Fujihara K, Miwa H, Tamamaki N, Yanagawa Y, Mushiake H.
  • Journal Title: Front Neural Circuits. Volume: 3 Pages: 6-6
  • DOI: 10.3389/fncir.2015.00006
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Transcriptional regulation of glutamic acid decarboxylase in the male mouse amygdala by dietary phytoestrogens (2015)
  • Author(s): Sandhu KV, Yanagawa Y et al.
  • Journal Title: J Neuroendocrinol. Volume: 27 Issue: 4 Pages: 285-292
  • DOI: 10.1111/jne.12262
  • Peer Reviewed / Acknowledgement Compliant
• [Presentation] Generation and characterization of glutamate decarboxylase knockout rats. (2018)
  • Author(s): Fujihara K, Kakizaki T, Miyata S, Watanabe M, Ohshiro T, Mushiake H, Miyasaka Y, Mashimo T, Yanagawa Y.
  • Organizer: 第95回日本生理学会大会
• [Presentation] Lethal phenotype and seizures in glutamate decarboxylase 65 knockout rats. (2017)
  • Author(s): Yanagawa Y, Kakizaki T, Watanabe M.
  • Organizer: 第94回日本生理学会大会
  • Place of Presentation: 浜松
  • Year and Date: 2017-03-28
• [Presentation] TALENを用いたゲノム編集で作製したグルタミン酸脱炭酸酵素65ノックアウトラットの解析 (2017)
  • Author(s): 柳川右千夫、柿崎利和、渡辺雅彦
  • Organizer: 日本ゲノム編集学会第2回大会
• [Presentation] Premature lethality in glutamate decarboxylase 65-deficient rats. (2017)
  • Author(s): Kakizaki T, Watanabe M, Yanagawa Y.
  • Organizer: 第40回日本神経科学大会
• [Presentation] A genetic mouse model of GABAergic dysfunction in schizophrenia. (2016)
  • Author(s): Yanagawa Y.
  • Organizer: 第39回日本神経科学大会
  • Place of Presentation: 横浜
  • Year and Date: 2016-07-20
• [Presentation] Phenotypic comparison between glutamate decarboxylase 65-deficient mice and rats. (2016)
  • Author(s): Kakizaki T, Watanabe M, Yanagawa Y.
  • Organizer: 第39回日本神経科学大会
  • Place of Presentation: 横浜
  • Year and Date: 2016-07-20
• [Presentation] Comparison between glutamate decarboxylase 65 knockout mice and rats. (2016)
  • Author(s): Kakizaki T, Watanabe M, Yanagawa Y.
  • Organizer: 10th FENS meeting
  • Place of Presentation: Copenhagen, Denmark.
  • Year and Date: 2016-07-02
  • Int'l Joint Research
• [Presentation] A novel role of GABA in the release of CRH in the hypothalamo-pituitary pathway (2015)
  • Author(s): Kakizawa K, Watanabe M, Yanagawa Y, Oki Y, Fukuda A.
  • Organizer: 第38回日本神経科学大会
  • Place of Presentation: 神戸コンベンションセンター(兵庫県神戸市)
  • Year and Date: 2015-07-28
• [Presentation] Cre-dependent tdTomato reporter mouse lines to visualize inhibitory neuron (2015)
  • Author(s): Kaneko R, Takatsuru Y, Yanagawa Y.
  • Organizer: 第38回日本神経科学大会
  • Place of Presentation: 神戸コンベンションセンター(兵庫県神戸市)
  • Year and Date: 2015-07-28
• [Presentation] GABAニューロンを標的とした遺伝子改変マウスの開発 (2014)
  • Author(s): 柳川右千夫
  • Organizer: 第18回活性アミンに関するワークショップ
  • Place of Presentation: 高松
  • Year and Date: 2014-08-30
  • Invited
• [Remarks] 群馬大学 大学院医学系研究科 医学部 医学科 大学院医学系研究科 医科学専攻 組織 遺伝発達行動学
  • URL: http://www.med.gunma-u.ac.jp/med-organization/neurosci/neurosci-development/106.html
• [Remarks] 群馬大学大学院医学系研究科 脳神経発達統御学講座 遺伝発達行動学分野
  • URL: http://genbehavneuro.dept.med.gunma-u.ac.jp/Yanagawa_Lab/Home.html