Function of a novel male-specific gene in Aedes aegypti

埃及伊蚊中一种新的雄性特异性基因的功能

• 批准号: 8856494
• 负责人: Zhijian Jake Tu
• 金额: $ 19.99万
• 依托单位: VIRGINIA POLYTECHNIC INST AND ST UNIV
• 依托单位国家: 美国
• 财政年份: 2014
• 资助国家: 美国
• 起止时间: 2014-06-01 至 2017-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8856494
• 关键词: Adult; Aedes; Alternative Splicing; Anopheles Genus; Attention; BCL2/Adenovirus E1B 19kd Interacting Protein 3-Like; Biology; Bite; Blood; Chikungunya virus; Chromosomes; Chromosomes, Human, Pair 1; Complex; Culex (Genus); Culicidae; Dengue; Development; Disease; Disease Outbreaks; Distant; Drosophila genus; Ectopic Expression; Embryo; Equilibrium; Female; Florida; Future; Gene Expression Profile; Genes; Genetic; Genetic Recombination; Genome; Genomic DNA; Genomics; Health; Homologous Gene; Incidence; Insecta; Insecticide Resistance; Knock-out; Larva; Lead; Location; Measures; Methods; Minor Lymphocyte Stimulatory Loci; Molecular; Monitor; Mosquito Control; Mosquito-borne infectious disease; Names; Other Genetics; Outcome; Pathway interactions; Play; Population; Prevention; Production; Protein Isoforms; Proteins; Publications; Pupa; RNA Recognition Motif; RNA Splicing; RNA-Binding Proteins; Reporting; Research; Risk; Role; Specificity; Sterility; Techniques; Technology; Testing; Testis; Tissues; Transgenic Organisms; World Health Organization; X Chromosome; Y Chromosome; Yellow Fever; base; combat; cost effective; digital; feeding; fly; functional genomics; genetic approach; mRNA Precursor; male; novel; offspring; pathogen; physical mapping; practical application; protein complex; sex; sex determination; simulation; vaccine trial; vector; vector control

DESCRIPTION (provided by applicant): Aedes aegpyti is a major vector of dengue, yellow fever, and chikungunya viruses. According to the World Health Organization, the global incidence of dengue has increased dramatically in recent decades and nearly half of the world population is now at risk. There is no specific treatment for dengue and current prevention depends solely on effective vector control. However, vector control methods are under threat as insecticide-resistance increases. New strategies to combat dengue and other mosquito-borne diseases are urgently needed. Several genetic strategies to suppress or replace vector populations are being explored. Since only female mosquitoes bite and transmit pathogens, the release of males is preferred and possibly required for implementation of these strategies. A better understanding of the sex-determination pathway will provide novel targets for interference and lead to several practical applications. For example, transgenic lines may be obtained that confer conditional female lethality, which will provide more cost-effective and scalable production of male-only mosquitoes than current approaches. Release of such transgenic males is more effective at achieving population reduction than sterile male release. However, little is known about sex determination in mosquitoes except for a few highly conserved genes such as doublesex (dsx) and transformer2 (tra2). Male development in Aedes mosquitos is initiated by a dominant male-determining locus (M-locus) located on the chromosome 1. However, no M-locus genes have been reported. We recently identified a novel male-specific gene in Ae. aegypti, which we named nix. Physical mapping places nix at the M-locus and nix genomic DNA was never detected in any female. No recombination was detected between nix and the M-locus when more than 5000 offspring were screened. Nix is expressed in the early embryo, larvae, pupae, and adult male testis, but not in any adult female tissues. Furthermore, the predicted NIX protein is an RNA-binding protein which may be involved in splicing. We hypothesize that nix plays an important role in sexual differentiation in Ae. aegypti. To test the hypothesis during thi exploratory R21 project, we will determine the effect of both ectopic expression (Aim 1) and knockout (Aim 2) of the nix gene. To determine the outcome of the two complementary approaches, we will monitor general phenotypic and molecular changes and pay close attention to those related to sexual differentiation. We anticipate extending our research beyond this R21 to investigate the mechanism of nix function and develop mosquito control applications through manipulation of the nix gene or its partners.

描述（由申请人提供）：埃及伊蚊是登革热、黄热病和基孔肯雅病毒的主要媒介。据世界卫生组织称，近几十年来，登革热的全球发病率急剧上升，世界上近一半的人口现在处于危险之中。没有针对登革热的特异性治疗方法，目前的预防完全取决于有效的病媒控制。然而，随着杀虫剂耐药性的增加，病媒控制方法正受到威胁。迫切需要新的战略来防治登革热和其他蚊媒疾病。目前正在探索几种抑制或替代病媒种群的遗传策略。由于只有雌蚊叮咬和传播病原体，因此释放雄蚊是可取的，而且可能是实施这些战略所必需的。对性别决定途径的更好理解将为干扰提供新的靶点，并导致一些实际应用。例如，可以获得具有条件的雌性致死性的转基因品系，这将比目前的方法提供更具成本效益和可扩展的纯雄性蚊子生产。释放这种转基因雄性比释放不育雄性在实现种群减少方面更有效。然而，除了一些高度保守的基因，如双性（dsx）和transformer2 （tra2）外，对蚊子的性别决定知之甚少。伊蚊的雄性发育是由位于1号染色体上的显性雄性决定位点（m位点）启动的。然而，m位点基因尚未被报道。我们最近在伊蚊中发现了一种新的雄性特异性基因。埃及伊蚊，我们称之为尼克斯。物理图谱显示，在任何女性中，m位点和基因组DNA都没有被检测到。在对5000多个后代进行筛选时，未发现nix和m位点之间存在重组。Nix在早期胚胎、幼虫、蛹和成年雄性睾丸中表达，但在任何成年雌性组织中都不表达。此外，预测的NIX蛋白是一种rna结合蛋白，可能参与剪接。我们假设nix在伊蚊的性别分化中起重要作用。蚊。为了在这个探索性R21项目中验证这一假设，我们将确定nix基因的异位表达（Aim 1）和敲除（Aim 2）的影响。为了确定这两种互补方法的结果，我们将监测一般的表型和分子变化，并密切关注与性别分化有关的变化。我们期望将我们的研究扩展到R21之外，以研究nix功能的机制，并通过操纵nix基因或其伴侣来开发蚊虫控制应用。

项目成果

SEX DETERMINATION. A male-determining factor in the mosquito Aedes aegypti.

• DOI: 10.1126/science.aaa2850
• 发表时间: 2015-06-12
• 期刊: Science (New York, N.Y.)
• 作者: Hall AB;Basu S;Jiang X;Qi Y;Timoshevskiy VA;Biedler JK;Sharakhova MV;Elahi R;Anderson MA;Chen XG;Sharakhov IV;Adelman ZN;Tu Z
• 通讯作者: Tu Z