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）：艾德斯Aegpyti是登革热，黄热病和基孔肯雅病毒的主要媒介。根据世界卫生组织的数据，近几十年来，全球登革热的发生率急剧增加，而世界近一半的人口正处于危险之中。没有针对登革热的特定治疗方法，而当前的预防仅取决于有效的向量控制。但是，随着抗杀虫剂的抗性增加，矢量控制方法受到威胁。迫切需要采取新的策略来打击登革热和其他蚊子传播疾病。正在探索几种抑制或取代媒介种群的遗传策略。由于只有雌性蚊子咬合并传播病原体，因此雄性的释放是优选的，可能需要实施这些策略。更好地了解性别确定的途径将为干扰提供新的目标，并导致几种实际应用。例如，可以获得有条件的女性致死率的转基因线，这将提供比目前的方法更具成本效益和可扩展性的纯种蚊子的生产。与无菌男性释放相比，这种转基因雄性的释放在减少人口方面更有效。然而，除了一些高度保守的基因，例如Doublesex（DSX）和Transformer2（TRA2）之外，对蚊子中的性别确定知之甚少。埃德斯蚊子中的男性发育是由位于1号染色体上的主要男性确定基因座（M-Locus）引发的。但是，尚无报告的M-Locus基因。我们最近在AE中确定了一个新型男性基因。埃及，我们将其命名为Nix。物理映射将NIX放置在M-Locus，在任何雌性中从未检测到NIX基因组DNA。当筛选超过5000个后代时，在NIX和M-Locus之间未检测到重组。 Nix在早期的胚胎，幼虫，pup和成年男性睾丸中表达，但在任何成年女性组织中都不表达。此外，预测的Nix蛋白是一种可能参与剪接的RNA结合蛋白。我们假设Nix在AE的性别分化中起着重要作用。埃及。为了测试Thi探索性R21项目期间的假设，我们将确定NIX基因的异位表达（AIM 1）和敲除（AIM 2）的影响。为了确定两种互补方法的结果，我们将监控一般的表型和分子变化，并密切注意与性别分化有关的人。我们预计将我们的研究扩展到该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子控制应用。

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