The physiological roles of vesicular GABA transporter during embryonic development : a study using knockout mice

Saito, Kenzi; Kakizaki, Toshikazu; Hayashi, Ryotaro; Nishimaru, Hiroshi; Furukawa, Tomonori; Nakazato, Yoichi; Takamori, Shigeo; Ebihara, Satoe; Uematsu, Masakazu; Mishina, Masayoshi; Miyazaki, Jun-ichi; Yokoyama, Minesuke; Konishi, Shiro; Inoue, Koichi; Fukuda, Atsuo; Fukumoto, Manabu; Nakamura, Kenji; Obata, Kunihiko; Yanagawa, Yuchio

doi:info:doi/10.1186/1756-6606-3-40

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タイトル	The physiological roles of vesicular GABA transporter during embryonic development : a study using knockout mice
著者	Saito, Kenzi Saito, Kenzi
	Kakizaki, Toshikazu Kakizaki, Toshikazu
	Hayashi, Ryotaro Hayashi, Ryotaro
	Nishimaru, Hiroshi Nishimaru, Hiroshi
	Furukawa, Tomonori Furukawa, Tomonori
	Nakazato, Yoichi Nakazato, Yoichi
	Takamori, Shigeo Takamori, Shigeo
	Ebihara, Satoe Ebihara, Satoe
	Uematsu, Masakazu Uematsu, Masakazu
	Mishina, Masayoshi Mishina, Masayoshi
	Miyazaki, Jun-ichi Miyazaki, Jun-ichi
	Yokoyama, Minesuke Yokoyama, Minesuke
	Konishi, Shiro Konishi, Shiro
	Inoue, Koichi Inoue, Koichi
	Fukuda, Atsuo Fukuda, Atsuo
	Fukumoto, Manabu Fukumoto, Manabu
	Nakamura, Kenji Nakamura, Kenji
	Obata, Kunihiko Obata, Kunihiko
	Yanagawa, Yuchio Yanagawa, Yuchio
抄録	Background: The vesicular GABA transporter (VGAT) loads GABA and glycine from the neuronal cytoplasm into synaptic vesicles. To address functional importance of VGAT during embryonic development, we generated global VGAT knockout mice and analyzed them.
	Results: VGAT knockouts at embryonic day (E) 18.5 exhibited substantial increases in overall GABA and glycine, but not glutamate, contents in the forebrain. Electrophysiological recordings from E17.5-18.5 spinal cord motoneurons demonstrated that VGAT knockouts presented no spontaneous inhibitory postsynaptic currents mediated by GABA and glycine. Histological examination of E18.5 knockout fetuses revealed reductions in the trapezius muscle, hepatic congestion and little alveolar spaces in the lung, indicating that the development of skeletal muscle, liver and lung in these mice was severely affected.
	Conclusion: VGAT is fundamental for the GABA- and/or glycine-mediated transmission that supports embryonic development. VGAT knockout mice will be useful for further investigating the roles of VGAT in normal physiology and pathophysiologic processes.
公開者	BioMed Central
掲載誌名	Molecular Brain
巻	3
号	40
開始ページ	1
終了ページ	13
刊行年月	2010-12-30
ISSN	17566606
DOI	info:doi/10.1186/1756-6606-3-40
URL	http://hdl.handle.net/11094/23112
権利情報	Copyright © 2010 Saito et al; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
言語	英語
カテゴリ	学術雑誌論文 Journal Article

著者版フラグ	publisher
NII資源タイプ	学術雑誌論文
ローカル資源タイプ	学術雑誌論文
dcmi資源タイプ	text
DCTERMS.bibliographicCitation	Molecular Brain.3(40) P.1-P.13
DC.title	The physiological roles of vesicular GABA transporter during embryonic development : a study using knockout mice
DC.creator	Saito, Kenzi
	Kakizaki, Toshikazu
	Hayashi, Ryotaro
	Nishimaru, Hiroshi
	Furukawa, Tomonori
	Nakazato, Yoichi
	Takamori, Shigeo
	Ebihara, Satoe
	Uematsu, Masakazu
	Mishina, Masayoshi
	Miyazaki, Jun-ichi
	Yokoyama, Minesuke
	Konishi, Shiro
	Inoue, Koichi
	Fukuda, Atsuo
	Fukumoto, Manabu
	Nakamura, Kenji
	Obata, Kunihiko
	Yanagawa, Yuchio
DC.publisher	BioMed Central
DC.language" scheme="DCTERMS.RFC1766	英語
DCTERMS.issued" scheme="DCTERMS.W3CDTF	2010-12-30
DC.identifier	info:doi/10.1186/1756-6606-3-40
DC.identifier" scheme="DCTERMS.URI	http://hdl.handle.net/11094/23112
DCTERMS.abstract	Background: The vesicular GABA transporter (VGAT) loads GABA and glycine from the neuronal cytoplasm into synaptic vesicles. To address functional importance of VGAT during embryonic development, we generated global VGAT knockout mice and analyzed them.
	Results: VGAT knockouts at embryonic day (E) 18.5 exhibited substantial increases in overall GABA and glycine, but not glutamate, contents in the forebrain. Electrophysiological recordings from E17.5-18.5 spinal cord motoneurons demonstrated that VGAT knockouts presented no spontaneous inhibitory postsynaptic currents mediated by GABA and glycine. Histological examination of E18.5 knockout fetuses revealed reductions in the trapezius muscle, hepatic congestion and little alveolar spaces in the lung, indicating that the development of skeletal muscle, liver and lung in these mice was severely affected.
	Conclusion: VGAT is fundamental for the GABA- and/or glycine-mediated transmission that supports embryonic development. VGAT knockout mice will be useful for further investigating the roles of VGAT in normal physiology and pathophysiologic processes.
DC.rights	Copyright © 2010 Saito et al; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
citation_title	The physiological roles of vesicular GABA transporter during embryonic development : a study using knockout mice
citation_author	Saito, Kenzi
	Kakizaki, Toshikazu
	Hayashi, Ryotaro
	Nishimaru, Hiroshi
	Furukawa, Tomonori
	Nakazato, Yoichi
	Takamori, Shigeo
	Ebihara, Satoe
	Uematsu, Masakazu
	Mishina, Masayoshi
	Miyazaki, Jun-ichi
	Yokoyama, Minesuke
	Konishi, Shiro
	Inoue, Koichi
	Fukuda, Atsuo
	Fukumoto, Manabu
	Nakamura, Kenji
	Obata, Kunihiko
	Yanagawa, Yuchio
citation_publisher	BioMed Central
citation_language	英語
citation_date	2010-12-30
citation_journal_title	Molecular Brain
citation_volume	3
citation_issue	40
citation_firstpage	1
citation_lastpage	13
citation_issn	17566606
citation_doi	info:doi/10.1186/1756-6606-3-40
citation_public_url	http://hdl.handle.net/11094/23112

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