REGULATION OF PERIPHERAL NERVE-SPECIFIC NA CHANNEL, PN1

这项研究的长期目标是了解 调节外周组织和组织的特异性表达 神经系统特异性钠通道，PN1。NA通道，以 周围神经系统(PNS)神经元的轴突和胞体 这在很大程度上导致了这些细胞的电兴奋。 PN1Na通道具有以下独特的特性：第一，它是 仅有的主要在PNS中表达的基因；第二，PN1 在Brief(1分钟)的基础上迅速大幅上调暴露于 神经生长因子(NGF)和干扰素-γ(IFN-γ)的研究进展 未知的机制。我们的研究计划是：1)利用基因和 鉴定PN1调节DNA元件的生化技术 对报告基因PN1表达模式的研究 几个细胞系。2)确定发病机制--即刻早期基因和 反应元件-NGF和IFNGamma上调PN1的反应元件。这个 本实验室研制的酵母菌One杂交筛选将用于分离 即刻早期基因。3)测试在1和2中隔离的构造 他们有能力通过创造在体内驱动报告基因的表达 表达不同结构的转基因小鼠。来自这些的结果 实验应该适用于实验性或治疗性的 背景，以驱动基因表达，特别是PNS。

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.