KDR MUTATIONS IN THE COCKROACH

这项研究的长期目标是了解分子基础 蟑螂对杀虫剂的抗药性。 蟑螂是一种主要的 作为人类病原体的载体和主要威胁人类健康的 室内过敏源和急性哮喘病因。 战略 蟑螂和其他害虫的控制主要依靠 使用杀虫剂。 拟除虫菊酯是一大类 具有高杀虫活性和相对低杀虫活性的杀虫剂， 哺乳动物毒性 然而，大量使用拟除虫菊酯导致了 在许多害虫种群中选择抗性品系。先前 对拟除虫菊酯抗性德国蟑螂品系Ectiban的研究， R，表明该菌株的拟除虫菊酯抗性机制（KDR） 可能是由于钠离子通道基因突变所致。 最近编码Ectiban-R的帕拉基因的cDNA和遗传学上的 已克隆了相关的拟除虫菊酯敏感菌株CSMA， 测序 序列比较揭示了一个单一的氨基酸变化，从 ParaCSMA中的L993至ParaEctiban-R中的F993。 发现F993突变 在大多数拟除虫菊酯抗性蟑螂品系中，其中一些还 具有额外的KDR相关的帕拉基因突变。 表征 这些KDR相关的帕拉基因突变对钠的影响 通道特性和钠通道与拟除虫菊酯的相互作用 杀虫剂，提出了以下三个具体目标：1） 野生型和突变型帕拉钠的反应表征 拟除虫菊酯和位点2神经毒素的通道; 2） 野生型和突变型帕拉钠通道的功能特性;和 3)拟除虫菊酯与野生型和突变型帕拉结合的表征 钠离子通道 从这个项目中获得的知识将 这对保护一整类害虫控制 防治主要城市虫害和进一步 通过更好地了解分子水平， 钠通道和拟除虫菊酯之间的相互作用。

The long-term goal of this research is to understand the molecular basis of insecticide resistance in the cockroach. The cockroach is a major threat to human health as a carrier of human pathogens and a major source of indoor allergens and cause of acute asthma. Strategies for the control of cockroaches and other insect pests rely heavily on the application of insecticides. Pyrethroids are a large class of insecticides that possess high insecticidal activity and relative low mammalian toxicity. The heavy use of pyrethroids, however, led to rapid selection of resistant strains in many insect pest populations. Previous studies with the pyrethroid-resistant German cockroach strain, Ectiban- R, suggest that the pyrethroid resistance mechanism (kdr) in this strain is likely due to a mutation(s) in the para sodium channel gene. Recently cDNAs encoding para genes from Ectiban-R and a genetically related pyrethroid-susceptible strain, CSMA, have been cloned and sequenced. Sequence comparison reveals a single amino acid change, from L993 in ParaCSMA to F993 in ParaEctiban-R. The F993 mutation was found in most pyrethroid-resistant cockroach strains, some of which also possess additional kdr-associated para gene mutations. To characterize the effects of these kdr-associated para gene mutations on sodium channel properties and sodium channel interaction with pyrethroid insecticides, the following three specific aims are proposed: 1) Characterization of the responses of wild-type and mutant Para sodium channels to pyrethroids and site 2 neurotoxins; 2) Examination of functional properties of wild-type and mutant Para sodium channels; and 3) Characterization of pyrethroid binding to wild-type and mutant Para sodium channels. Knowledge gained from this project will have significant implications for preserving a whole class of pest control chemicals for the control of major urban insect pests and for further enhancing its efficacy through a better understanding of the molecular interactions between sodium channels and pyrethroids.