title: The physiological roles of vesicular GABA transporter during embryonic development: a study using knockout mice.
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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Genetic and Behavioral Neuroscience, Gunma University Graduate School of Medicine, Maebashi, Japan.
authors.forename: Kenzi
authors.initials: K
authors.lastname: Saito
authors.forename: Toshikazu
authors.initials: T
authors.lastname: Kakizaki
authors.forename: Ryotaro
authors.initials: R
authors.lastname: Hayashi
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Nishimaru
authors.forename: Tomonori
authors.initials: T
authors.lastname: Furukawa
authors.forename: Yoichi
authors.initials: Y
authors.lastname: Nakazato
authors.forename: Shigeo
authors.initials: S
authors.lastname: Takamori
authors.forename: Satoe
authors.initials: S
authors.lastname: Ebihara
authors.forename: Masakazu
authors.initials: M
authors.lastname: Uematsu
authors.forename: Masayoshi
authors.initials: M
authors.lastname: Mishina
authors.forename: Jun-ichi
authors.initials: J
authors.lastname: Miyazaki
authors.forename: Minesuke
authors.initials: M
authors.lastname: Yokoyama
authors.forename: Shiro
authors.initials: S
authors.lastname: Konishi
authors.forename: Koichi
authors.initials: K
authors.lastname: Inoue
authors.forename: Atsuo
authors.initials: A
authors.lastname: Fukuda
authors.forename: Manabu
authors.initials: M
authors.lastname: Fukumoto
authors.forename: Kenji
authors.initials: K
authors.lastname: Nakamura
authors.forename: Kunihiko
authors.initials: K
authors.lastname: Obata
authors.forename: Yuchio
authors.initials: Y
authors.lastname: Yanagawa
mesh_terms: D000818:Animals; D002972:Cleft Palate / Q000235:genetics; D047108:Embryonic Development; D005260:Female; D005838:Genotype; D005968:Glutamate Decarboxylase / Q000235:genetics; D018698:Glutamic Acid / Q000378:metabolism; D005998:Glycine / Q000378:metabolism; D006554:Hernia, Umbilical / Q000235:genetics; D008099:Liver / Q000166:cytology / Q000378:metabolism / Q000473:pathology; D008168:Lung / Q000166:cytology / Q000378:metabolism / Q000473:pathology; D051379:Mice; D018345:Mice, Knockout; D018482:Muscle, Skeletal / Q000166:cytology / Q000378:metabolism / Q000473:pathology; D018408:Patch-Clamp Techniques; D011247:Pregnancy; D009435:Synaptic Transmission / Q000502:physiology; D050495:Vesicular Inhibitory Amino Acid Transport Proteins / Q000235:genetics* / Q000378:metabolism*; D005680:gamma-Aminobutyric Acid / Q000378:metabolism
chemical_list: D050495:Vesicular Inhibitory Amino Acid Transport Proteins; C493406:vesicular GABA transporter; D018698:Glutamic Acid; D005680:gamma-Aminobutyric Acid; D005968:Glutamate Decarboxylase; C402565:glutamate decarboxylase 1; D005998:Glycine