Abstract

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.

Details

Title
The physiological roles of vesicular GABA transporter during embryonic development: a study using knockout mice
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
Pages
40
Publication year
2010
Publication date
2010
Publisher
BioMed Central
e-ISSN
1756-6606
Source type
Scholarly Journal
Language of publication
English
DOI
https://doi.org/10.1186/1756-6606-3-40
ProQuest document ID
902454165
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.