Glutamate transporter EAAC-1-deficient mice develop dicarboxylic aminoaciduria and behavioral abnormalities but no neurodegeneration
Glutamate transporter EAAC-1-deficient mice develop dicarboxylic aminoaciduria and behavioral abnormalities but no neurodegeneration
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DOI：
10.1093/emboj/16.13.3822
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发表时间：
1997-07-01
期刊：
影响因子：
11.4
通讯作者：
Stoffel, W
中科院分区：
文献类型：
--
作者：
Peghini, P;Janzen, J;Stoffel, W
四种L-谷氨酸神经递质转运体，三种Na+依赖的GLAST-1、GLT-1和EAAC-1，以及Cl-依赖的EAAT-4，形成了一个新的结构相关的质膜整合蛋白家族，在中枢神经系统中具有不同的分布。它们可能在神经传递过程中调节突触L-谷氨酸浓度方面具有关键作用，并被认为可防止谷氨酸神经毒性。为了研究也在肾脏和小肠中表达的神经元EAAC-1的特定生理和病理生理作用，我们产生了两个独立的缺乏EAAC-1的小鼠系，eaac-1（-/-）小鼠发展为二羧酸氨基酸尿症。在>12个月的时间内没有观察到神经变性，但纯合突变体显示出显著降低的自发运动活性。
Four L-glutamate neurotransmitter transporters, the three Na+-dependent GLAST-1, GLT-1 and EAAC-1, and the Cl--dependent EAAT-4, form a new family of structurally related integral plasma membrane proteins with different distribution in the central nervous system. They may have pivotal functions in the regulation of synaptic L-glutamate concentration during neurotransmission and are believed to prevent glutamate neurotoxicity. To investigate the specific physiological and pathophysiological role of the neuronal EAAC-1, which is also expressed in kidney and small intestine, we have generated two independent mouse lines lacking EAAC-1, eaac-1(-/-) mice develop dicarboxylic aminoaciduria. No neurodegeneration has been observed during a period of >12 months, but homozygous mutants display a significantly reduced spontaneous locomotor activity.