KDR MUTATIONS IN THE COCKROACH

蟑螂的 KDR 突变

• 批准号: 6490186
• 负责人: KE DONG
• 金额: $ 15.22万
• 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/6490186
• 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。 蟑螂是一大 作为人类病原体的携带者和主要威胁人类健康的 室内过敏原的来源和急性哮喘的原因。 策略 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 具有较高杀虫活性且相对较低的杀虫剂 哺乳动物毒性。 然而，拟除虫菊酯的大量使用导致迅速 在许多害虫种群中选择抗性菌株。以前的 对拟除虫菊酯耐药的德国小蠊菌株 Ectiban 进行的研究 R，表明该菌株的拟除虫菊酯抗性机制（kdr） 可能是由于对钠通道基因的突变造成的。 最近编码 Ectiban-R 的副基因的 cDNA 和基因 相关拟除虫菊酯敏感菌株 CSMA 已被克隆并 已测序。 序列比较揭示了单个氨基酸的变化，从 ParaCSMA 中的 L993 到 ParaEctiban-R 中的 F993。 发现F993突变 在大多数对拟除虫菊酯具有抗性的蟑螂品种中，其中一些还 具有额外的 kdr 相关副基因突变。 表征 这些与 kdr 相关的副基因突变对钠的影响 通道特性以及钠通道与拟除虫菊酯的相互作用 杀虫剂，提出以下三个具体目标：1） 野生型和突变型对钠反应的表征 拟除虫菊酯和位点 2 神经毒素的通道； 2）检查 野生型和突变型Para钠通道的功能特性；和 3) 拟除虫菊酯与野生型和突变型 Para 结合的表征 钠通道。 从这个项目中获得的知识将有 对于维护整个害虫防治类别具有重大意义 用于控制主要城市害虫和进一步防治的化学品 通过更好地了解分子机制来提高其功效 钠通道和拟除虫菊酯之间的相互作用。