KDR MUTATIONS IN THE COCKROACH

蟑螂的 KDR 突变

• 批准号: 6138656
• 负责人: KE DONG
• 金额: $ 14.34万
• 依托单位: MICHIGAN STATE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1999
• 资助国家: 美国
• 起止时间: 1999-01-01 至 2002-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6138656
• 关键词: Xenopus oocyte; alternatives to animals in research; cockroach; electrophysiology; gene mutation; genetic strain; insecticide biological effect; insecticide resistance; mathematical model; molecular cloning; molecular genetics; neurotoxins; nucleic acid sequence; pest control; pesticide interaction; phenotype; pyrethroid; receptor binding; sodium channel; voltage /patch clamp

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.

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 对人类健康的威胁是人类病原体的携带者和主要 室内过敏原来源和急性哮喘的原因。战略以实现 蟑螂和其他害虫的控制在很大程度上依赖于 杀虫剂的应用。拟除虫菊酯是一大类拟除虫菊酯 杀虫活性高、杀虫活性相对较低的杀虫剂 哺乳动物的毒性。然而，大量使用拟除虫菊酯导致了 多种害虫种群抗性品系的选育。上一首 对抗拟除虫菊酯德国蟑螂品种Ectiban的研究- R，提示该菌株对拟除虫菊酯的抗性机制(Kdr)。 可能是由于对钠通道基因突变(S)所致。 最近编码ECTIBAN-R的parA基因的cDNA和一个遗传上的 相关的拟除虫菊酯敏感株CSMA已被克隆并 已排序。序列比较揭示了单一氨基酸的变化，从 ParaCSMA中的L993到ParaEctiban-R中的F993。发现了F993突变 在大多数抗拟除虫菊酯蟑螂品种中，其中一些还 具有额外的kdr相关的副基因突变。刻画 这些kdr相关的副基因突变对钠的影响 拟除虫菊酯通道特性及其与钠通道的相互作用 对于杀虫剂，提出了以下三个具体目标：1) 野生型和突变型对映体的反应特性 拟除虫菊酯和第2位神经毒素的通道；2)检验 野生型和突变型副钠通道的功能特性；以及 3)拟除虫菊酯与野生型和突变型拟除虫菊酯结合特性 钠离子通道。从这个项目中获得的知识将会有 对保留整个虫害防治类别的重大影响 用于控制城市主要害虫的化学品和进一步 通过更好地了解分子来增强其疗效 拟除虫菊酯与钠通道的相互作用。