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

The physiological roles of vesicular GABA transporter during embryonic development: a study using knockout mice.
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DOI:
10.1186/1756-6606-3-40
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发表时间:
2010-12-30
期刊:
影响因子:
3.6
通讯作者:
Yanagawa Y
Yanagawa Y
中科院分区:
医学3区
文献类型:
--
作者:
Saito K;Kakizaki T;Hayashi R;Nishimaru H;Furukawa T;Nakazato Y;Takamori S;Ebihara S;Uematsu M;Mishina M;Miyazaki J;Yokoyama M;Konishi S;Inoue K;Fukuda A;Fukumoto M;Nakamura K;Obata K;Yanagawa Y

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囊泡GABA转运体(VGAT)将GABA和甘氨酸从神经元细胞质装载到突触囊泡中。为了解决VGAT在胚胎发育过程中的功能重要性,我们产生了全局VGAT敲除小鼠并对其进行了分析。在胚胎第18.5天(E)VGAT敲除表现出前脑中GABA和甘氨酸总含量的显著增加,但谷氨酸含量没有增加。E17.5-18.5脊髓运动神经元的电生理记录表明,VGAT基因敲除不呈现由GABA和甘氨酸介导的自发抑制性突触后电流。E18.5基因敲除胎仔的组织学检查显示,这些小鼠的肌萎缩、肝充血和肺肺泡腔变小,表明这些小鼠的骨骼肌、肝和肺的发育受到严重影响。VGAT是支持胚胎发育的GABA和/或甘氨酸介导的传输的基础。VGAT基因敲除小鼠将有助于进一步研究VGAT在正常生理和病理生理过程中的作用。
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. 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. 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.
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