FOS - AN IMMEDIATE-EARLY TRANSCRIPTION FACTOR IN NEURONS

FOS - AN IMMEDIATE-EARLY TRANSCRIPTION FACTOR IN NEURONS
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DOI:
10.1002/neu.480260312
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发表时间:
1995-03-01
期刊:
JOURNAL OF NEUROBIOLOGY
影响因子:
--
通讯作者:
MORGAN, JI
MORGAN, JI
中科院分区:
其他
文献类型:
--
作者:
CURRAN, T;MORGAN, JI

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在过去的几年中,大量的证据已经积累了连接神经元激活事件的基因表达的调控。我们已经进行了c-fos在神经系统中的调节分析,以阐明参与刺激转录耦合的分子机制。c-fos基因被认为是编码转录因子的细胞即刻早期基因组的原型,这些基因被认为通过协调靶基因表达的改变来将细胞外引起的短期信号与细胞表型的长期变化偶联。几种动物癫痫发作模型已被用来证明在特定群体的神经元基因表达的激活,使用转基因小鼠的方法,基于foslacZ融合基因,我们现在证明c-fos表达和神经系统细胞死亡之间的关联。在手术损伤后和神经毒素暴露后观察到延迟和延长的诱导,该系统使我们能够首次确定负责体内神经元中基因表达诱导的DNA调控序列,此外,foslacZ转基因小鼠为鉴定对特定刺激有反应或对特定毒素敏感的细胞群提供了独特的资源。(C)1995年,John Wiley and Sons,Inc.
In the past several years a great deal of evidence has accumulated linking neuronal activation events to the regulation of gene expression. We have pursued an analysis of c-fos regulation in the nervous system to elucidate the molecular mechanisms involved in stimulus-transcription coupling. The c-fos gene can be viewed as an archetype of the set of cellular immediate-early genes encoding transcription factors, These genes are believed to function in coupling short-term signals elicited by extracellular to long-term changes in cellular phenotype by orchestrating alterations in target gene expression. Several animal seizure models have been used to demonstrate the activation of gene expression in specific populations of neurons, Using a transgenic mouse approach, based on a foslacZ fusion gene, we now demonstrate an association between c-fos expression and cell death in the nervous system. A delayed and protracted induction was observed following surgical lesion and in response to neurotoxin exposure, This system allows us to determine, for the first time, the DNA regulatory sequences that are responsible for the induction of gene expression in neurons in vivo, Furthermore, foslacZ transgenic mice provide a unique resource for identifying cell populations that respond to specific stimuli or that are susceptible to particular toxins. (C) 1995 John Wiley and Sons, Inc.