Deletion of the mouse glycine transporter 2 results in a hyperekplexia phenotype and postnatal lethality
Deletion of the mouse glycine transporter 2 results in a hyperekplexia phenotype and postnatal lethality
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DOI：
10.1016/s0896-6273(03)00673-1
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发表时间：
2003-11-13
期刊：
影响因子：
16.2
通讯作者：
Betz, H
中科院分区：
文献类型：
--
作者：
Gomeza, J;Ohno, K;Betz, H
甘氨酸转运子亚型2（GlyT2）定位于甘氨酸能神经元的轴突终末。缺乏GlyT2的小鼠在出生时是正常的，但在出生后的第二周期间发展出致命的神经运动缺陷，其类似于严重形式的人类过度兴奋（遗传性惊吓疾病），并且特征在于痉挛、震颤和不能正确。组织学和免疫学分析未能揭示解剖学或生化异常，但甘氨酸能微型抑制电流（mIPSC）的幅度显着降低舌下神经运动神经元和分离的脊髓神经元GlyT2缺陷小鼠。因此，出生后的GlyT2功能是至关重要的甘氨酸能神经末梢的突触囊泡的有效的递质加载，和GlyT2基因构成了一个候选的疾病基因在人类hyperekplexia患者。
The glycine transporter subtype 2 (GlyT2) is localized in the axon terminals of glycinergic neurons. Mice deficient in GlyT2 are normal at birth but during the second postnatal week develop a lethal neuromotor deficiency that resembles severe forms of human hyperekplexia (hereditary startle disease) and is characterized by spasticity, tremor, and an inability to right. Histological and immunological analyses failed to reveal anatomical or biochemical abnormalities, but the amplitudes of glycinergic miniature inhibitory currents (mIPSCs) were strikingly reduced in hypoglossal motoneurons and dissociated spinal neurons from GlyT2-deficient mice. Thus, postnatal GlyT2 function is crucial for efficient transmitter loading of synaptic vesicles in glycinergic nerve terminals, and the GlyT2 gene constitutes a candidate disease gene in human hyperekplexia patients.