Juvenile Hormone Receptor in Flies and Mosquitoes

性状（由申请人提供）：蜕皮甾酮和保幼激素（JH）是昆虫生殖和发育的主要内分泌调节剂。JH的作用机制比蜕皮甾酮的作用机制知之甚少，这主要是由于我们对JH受体和JH调节基因的认识不足。果蝇的甲氧普仑耐受基因bHLH-PAS参与了JH的作用，它可以作为理解JH在果蝇和果蝇中分子作用的关键。黑腹果蝇和蚊子。拟议的工作是一种遗传方法，将实现四个目标：首先，从埃及伊蚊的Met+同源基因将被分离和测序。AE.埃及伊蚊是一种被充分研究的疾病媒介，这项工作将开始了解蚊子中的JH受体。 其次，将进行与Met相互作用的突变体的增强子/抑制子筛选以确定JH受体复合物和相关蛋白。第三，将进行Met的点突变和缺失突变，以确定对该基因的功能至关重要的MET区域。最后，将通过DNA微阵列分析鉴定由JH转录控制的基因（JH靶基因）。这些基因的鉴定将有助于我们了解JH的作用，并在未来的工作将允许构建一个报告基因检测JH，以促进进一步的JH信号转导的分子分析。 这一工作对于了解昆虫JH受体的遗传结构具有重要意义。它将导致更好地了解杀虫剂甲氧普烯的作用和昆虫抗药性，该杀虫剂用于控制疾病的蚊子媒介。此外，更好地了解作为一个bHLH-PAS基因的Met将进一步我们的知识，这个家庭的转录调控因子，包括在人类中发现的同源基因。

DESCRIPTION (provided by the applicant): Ecdysterone and juvenile hormone (JH) are the primary endocrine regulators of reproduction and development in insects. The mechanism of action of JH is much more poorly understood than that of ecdysterone, due primarily to our dismal knowledge of the JH receptor and JH-regulated genes. The Methoprene-tolerant (Met) bHLH-PAS gene of Drosophila melanogaster is involved in the action of JH, and it can serve as a key to understanding the molecular action of this hormone in both D. melanogaster and mosquitoes. The proposed work is a genetic approach that will accomplish four objectives: First, the Met+ homologous gene from the aedine mosquito Aedes aegypti will be isolated and sequenced. Ae. aegypti is a well-studied disease vector, and this effort will begin an understanding of the JH receptor in mosquitoes. Second, an enhancer/suppressor screen of mutants that interact with Met will be carried out to define the JH receptor complex and related proteins. Third, both point and deletion mutagenesis of Met will be carried out to define the region(s) of MET critical for the functions of this gene. Finally, genes that are transcriptionally controlled by JH (JH target genes) will be identified by DNA micro-array analysis. Identification of these genes will help us understand JH roles and in future work will permit construction of a reporter gene assay for JH to facilitate further molecular analysis of JH signal transduction. This work will have significance for understanding the JH receptor in a genetically well-defined insect. It will lead to a better understanding of the action and insect resistance to the insecticide methoprene, which is used to control mosquito vectors of disease. In addition, a better understanding of Met as a bHLH-PAS gene will further our knowledge of this family of transcriptional regulators, including homologous genes found in humans.