A COMPREHENSIVE RESOURCE BASE OF C. ELEGANS K+ CHANNELS

描述(由申请人提供)： 线虫基因组包含一个由70多个成员组成的钾通道扩展基因家族。在这些基因中，有一组古老的保守的钾通道，在人类和果蝇中都有同源基因。在心脏生理学、神经功能、肾脏和消化疾病等不同领域工作的研究人员对这些保守基因中的许多都感兴趣。因此，线虫有潜力成为几乎所有可兴奋的膜和离子电流重要的领域的基础研究的有价值的模型系统。研究人员建议建立一个资源库，其中将包括适合哺乳动物细胞系和非洲爪哇卵母细胞功能表达的载体中的全长钾通道cDNA克隆，以及KO基因菌株的库存。支持这一资源基础的将是展示通道基本生物物理性质的研究、展示KO突变体表型的研究以及关于每个通道的细胞类型表达模式的信息。这一综合性项目的许多方面将直接指导哺乳动物的研究，并应提供一种适用于基础和应用研究的各种研究人员的替代模式系统。

DESCRIPTION (provided by applicant): The C. elegans genome contains an extended gene family of potassium channels consisting of more than seventy members. Among these genes are an ancient conserved "set" of potassium channels with orthologues in both humans and Drosophila. Many of these conserved genes are of interest to researchers working in fields as diverse as cardiac physiology, neurological function, and kidney and digestive disorders. Thus, C. elegans has the potential of being a valuable model system for basic research in virtually all fields where excitable membranes and ion currents are important. The investigators propose to create a resource base that will include full-length potassium channel cDNA clones in vectors suitable for functional expression in mammalian cell lines and Xenopus oocytes, and stocks of gene KO strains. Supporting this resource base will be studies showing the basic biophysical properties of the channels, studies showing the phenotypes of KO mutants and information on the cell-type expression patterns of each channel. Many aspects of this comprehensive project will directly guide studies in mammals and should offer an alternative model system applicable to a wide variety of researchers in both basic and applied research.