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

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, Yuchio Yanagawa

Research output: Contribution to journalArticlepeer-review

43 Citations (Scopus)

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.

Original languageEnglish
Article number40
JournalMolecular brain
Volume3
Issue number1
DOIs
Publication statusPublished - 2010

ASJC Scopus subject areas

  • Molecular Biology
  • Cellular and Molecular Neuroscience

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