REGULATION OF PERIPHERAL NERVE-SPECIFIC NA CHANNEL, PN1

周围神经特异性 NA 通道的调节，PN1

• 批准号: 2710307
• 负责人: Julia Eve Dallman
• 金额: $ 2.5万
• 依托单位: STATE UNIVERSITY NEW YORK STONY BROOK
• 依托单位国家: 美国
• 财政年份: 1998
• 资助国家: 美国
• 起止时间: 1998-12-01 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/2710307
• 关键词: PC12 cells; animal genetic material tag; gene induction /repression; genetic regulatory element; genetically modified animals; interferon gamma; laboratory mouse; neurotrophic factors; nucleic acid sequence; peripheral nervous system; reporter genes; sodium channel; voltage gated channel

The long-term goal of this research is to understand the mechanisms that regulate the temporal and tissue specific expression of the peripheral nervous system specific Na channel, PN1. Na channels, expressed in the axons and cell bodies of peripheral nervous system (PNS) neurons, are in large part responsible for making these cells electrically excitable. The PN1 Na channel has the following unique properties: first, it is one of the only genes expressed predominantly in the PNS; and second, PN1 is rapidly and dramatically upregulated upon brief (1 min.) exposure to nerve growth factor (NGF) and interferon gamma (IFNgamma) by an as yet unknown mechanism. Our research plan is to: 1) Use genetic and biochemical techniques to identify PN1 regulatory DNA elements that confer the PN1 expression pattern on reporter genes transfected into several cell lines. 2) Determine the mechanism-immediate early genes and response elements-by which PN1 is upregulated by NGF and IFNgamma. The yeast one hybrid screen developed In the Pls lab will be used to isolate immediate early genes. 3) Test the constructs isolated in 1 and 2 for their ability to drive expression of a reporter gene in vivo by creating transgenic mice expressing the different constructs. Results from these experiments should be applicable in an experimental or therapeutic context to drive gene expression specifically PNS.

这项研究的长期目标是了解 调节外周神经元的时间和组织特异性表达， 神经系统特异性钠通道PN 1。 Na通道，表达于 周围神经系统（PNS）神经元的轴突和细胞体， 在很大程度上负责使这些细胞电兴奋。 PN 1 Na通道具有以下独特性质：首先，它是一个 在PNS中主要表达的唯一基因;第二，PN 1 在短暂（1分钟）后迅速且显著地上调。暴露于 神经生长因子（NGF）和干扰素γ（IFN γ）， 未知机制 我们的研究计划是：1）利用遗传和 生物化学技术来鉴定PN 1调节DNA元件， 将PN 1表达模式赋予转染到 几种细胞系。2)确定机制-立即早期基因和 反应元件-通过该元件，PN 1被NGF和IFN γ上调。 的 在Pls实验室开发的酵母单杂交筛选将用于分离 早期基因3)测试1和2中分离的结构， 它们能够通过在体内产生 表达不同构建体的转基因小鼠。从这些 实验应适用于实验或治疗 背景驱动基因表达，特别是PNS。