Neurological dysfunctions in mice expressing different levels of the Q/R site-unedited AMPAR subunit GluR-B
Neurological dysfunctions in mice expressing different levels of the Q/R site-unedited AMPAR subunit GluR-B
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DOI：
10.1038/4561
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发表时间：
1999-01-01
影响因子：
25
通讯作者：
Seeburg, PH
中科院分区：
文献类型：
--
作者：
Feldmeyer, D;Kask, K;Seeburg, PH
我们产生了具有靶向AMPA受体（AMPAR） GluR-B亚基等位基因的小鼠突变体，这些突变体在功能上表达不同水平，并且缺乏Q/ r位点编辑。所有突变系都增加了锥体神经元的AMPAR钙通透性，其中一个突变系表现出这些通道的宏观电导升高。ampar介导的钙内流诱导海马锥体细胞连接中nmda受体不依赖的长期增强（LTP）。没有观察到钙触发的神经元死亡，但突变体有轻微到严重的神经功能障碍，包括癫痫和树突结构缺陷。Q/ r位点改变的GluR-B亚基转基因的影响独立揭示了癫痫易发表型与宏观电导增加相关。因此，GluR-B基因表达和Q/R位点编辑的变化可以影响兴奋性主神经元的关键结构和功能方面。
We generated mouse mutants with targeted AMPA receptor (AMPAR) GluR-B subunit alleles, functionally expressed at different levels and deficient in Q/R-site editing. All mutant lines had increased AMPAR calcium permeabilities in pyramidal neurons, and one showed elevated macroscopic conductances of these channels. The AMPAR-mediated calcium influx induced NMDA-receptor-independent long-term potentiation (LTP) in hippocampal pyramidal cell connections. Calcium-triggered neuronal death was not observed, but mutants had mild to severe neurological dysfunctions, including epilepsy and deficits in dendritic architecture. The seizure-prone phenotype correlated with an increase in the macroscopic conductance, as independently revealed by the effect of a transgene for a Q/R-site-altered GluR-B subunit. Thus, changes in GluR-B gene expression and Q/R site editing can affect critical architectural and functional aspects of excitatory principal neurons.