Molecular Brain (Dec 2010)

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
https://doi.org/10.1186/1756-6606-3-40
Journal volume & issue
Vol. 3, no. 1
p. 40

Abstract

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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.