KDR MUTATIONS IN THE COCKROACH

蟑螂的 KDR 突变

• 批准号: 2758473
• 负责人: KE DONG
• 金额: $ 13.89万
• 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/2758473
• 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 蟑螂中的杀虫剂耐药性。 蟑螂是主要的 威胁人类健康作为人类病原体的载体和主要的威胁 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严重依赖于 杀虫剂的应用。 拟除虫菊酯是一类 具有高杀虫活性和相对低的杀虫剂 哺乳动物的毒性。 但是，大量使用拟除虫毒导致 在许多害虫种群中选择抗性菌株。以前的 对拟除虫菊酯抗性的德国蟑螂菌株的研究，Ectiban- R，建议在该菌株中的拟除虫菊酯耐药机制（KDR） 可能是由于Para钠通道基因中的突变引起的。 最近，来自Ectiban-R的Para基因和遗传学的cDNA 相关的拟除虫菊酯敏感性菌株CSMA已被克隆，并且 测序。 序列比较表明，单个氨基酸的变化 L993在Paraectiban-R中的Paracsma至F993。 发现F993突变 在大多数拟甲虫素的蟑螂菌株中，其中一些也 具有额外的KDR相关PARA基因突变。 表征 这些与KDR相关的PARA基因突变对钠的影响 通道性质和钠通道与拟甲虫素的相互作用 杀虫剂，提出了以下三个特定目标：1） 野生型和突变体钠钠反应的表征 拟除虫菊酯和位点2神经毒素的通道； 2）检查 野生型和突变体钠钠通道的功能特性；和 3）表征拟除虫菊酯与野生型和突变体的结合 钠通道。 从这个项目中获得的知识将拥有 对保存整个害虫控制的重要意义 控制主要城市虫害的化学物质，并进一步 通过更好地理解分子来增强其疗效 钠通道与拟除虫菊酯之间的相互作用。