• Kenzi Saito, Toshikazu Kakizaki, Ryotaro Hayashi, Hiroshi Nishimaru, Tomonori Furukawa, Yoichi Nakazato, Shigeo Takamori, Satoe Ebihara, Masakazu Uematsu, Masayoshi Mishina, Jun-ichi Miyazaki, Minesuke Yokoyama, Shiro Konishi, Koichi Inoue, Atsuo Fukuda, Manabu Fukumoto, Kenji Nakamura, Kunihiko Obata, and Yuchio Yanagawa.
• Department of Genetic and Behavioral Neuroscience, Gunma University Graduate School of Medicine, Maebashi, Japan.
• Mol Brain. 2010 Jan 1;3:40.

BackgroundThe 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.ResultsVGAT 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.ConclusionVGAT 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.

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