EARLY-ONSET EPILEPSY AND POSTNATAL LETHALITY ASSOCIATED WITH AN EDITING-DEFICIENT GLUR-B ALLELE IN MICE
EARLY-ONSET EPILEPSY AND POSTNATAL LETHALITY ASSOCIATED WITH AN EDITING-DEFICIENT GLUR-B ALLELE IN MICE
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DOI：
10.1126/science.270.5242.1677
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发表时间：
1995-12-08
期刊：
影响因子：
56.9
通讯作者：
SPRENGEL, R
中科院分区：
文献类型：
--
作者：
BRUSA, R;ZIMMERMANN, F;SPRENGEL, R
GluR-B亚基586位的精氨酸残基使异聚体α-氨基-3-羟基-5-甲基-4-异恶唑丙酸酯（AMPA）敏感性谷氨酸受体通道对钙不可渗透。该精氨酸的密码子通过位点选择性腺苷编辑谷氨酰胺密码子在前体信使RNA（pre-mRNA）阶段引入。通过基因靶向工程改造的杂合小鼠含有一个编辑能力不强的GluR-B等位基因，合成了未经编辑的GluR-B亚基，并在主神经元和中间神经元中表达了AMPA受体，钙渗透性增加。这些小鼠在3周龄时发生癫痫发作并死亡，表明GluR-B前mRNA编辑对大脑功能至关重要。
The arginine residue at position 586 of the GluR-B subunit renders heteromeric alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionate (AMPA)-sensitive glutamate receptor channels impermeable to calcium. The codon for this arginine is introduced at the precursor messenger RNA (pre-mRNA) stage by site-selective adenosine editing of a glutamine codon. Heterozygous mice engineered by gene targeting to harbor an editing-incompetent GluR-B allele synthesized unedited GluR-B subunits and, in principal neurons and interneurons, expressed AMPA receptors with increased calcium permeability. These mice developed seizures and died by 3 weeks of age, showing that GluR-B pre-mRNA editing is essential for brain function.