媒介昆虫引起的传染病（虫媒病），如：疟疾、登革热和寨卡热，一直是严重危害人类健康的公共卫生问题。化学防治一直是媒介防制规划中的主要方法，然而大量使用杀虫剂导致媒介抗药性。全世界每年因抗性造成的损失达几十亿美元。抗性机制研究是媒介抗性治理的基础。近年来国内外研究者采用现代生物技术方法克隆筛选大量抗药性基因。如何从中筛选出最具价值的主效基因成为迫切需要解决的问题。申请人在国家自然科学基金项目资助下，应用新型生物技术eQTL，分析蚊抗性相关基因的调控网络，首次筛选获得抗性主效基因CppNJ-1。基于以上研究结果，申请人拟进一步采用体外表达降解和Crispr-cas9转基因蚊等技术深入研究主效基因CppNJ-1的抗性机理，并探讨其调控机制。本项目预期结果可望鉴定蚊抗药性主效基因，进一步阐明抗药性机理，为建立蚊现场抗药性检测和抗药性治理新方法提供科学依据，具有重要的科学意义和应用价值。

Vector-borne disease, such as: malaria, dengue fever and zika virus diseases, pose a major threat to public health, which account for 17% of the global communicable diseases. Vector control is a major method for the control and prevention of vector-borne diseases. Chemical control has been the main control intervention for vector-borne diseases. However, the wide use of insecticide has resulted in the emergence and spread of resistance in vector populations. The world's annual cost for insecticide resistance management is for at least a billion dollars per year. To fully understand the mechanism of insecticide resistance, investigators have cloned and screened a large number of resistant-associated genes by using modern biotechnology methods, such as microarray, amplified fragment length polymorphism, transcriptome analysis and isobaric tags for relative and absolute protein quantification. In the past 4-year granting period, using expression quantitative trait loci (eQTL), we have made significant progress in elucidating the core functional gene (Culex pipiens pallensNJ-1, CppNJ-1) for mosquito insecticide resistance. So, the central objective of this renewal application is to further investigate the resistance mechanism of CppNJ-1, using exogenous expression and degradation, generate transgenic mosquito using Crispr-cas9 technology. Moreover, we will further explore the regulatory mechanism for CppNJ-1. We anticipate that this research will significantly enhance our understanding of resistance to insecticides in mosquitoes, and facilitate the development of sensitive and reliable molecular methods for insecticide resistance surveillance, and for the rational management of insecticide resistance.