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A synthetic male-specific sterilization system using the mammalian pro-apoptotic factor in a malaria vector mosquito

机译:在疟疾媒介蚊子中使用哺乳动物促细胞凋亡因子的男性特异性合成灭菌系统

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摘要

Conditional cell death systems are useful for various aspects of basic science with a wide range of applications, including genetic pest control. We recently demonstrated that expression of the mammalian pro-apoptotic factor, B-cell leukaemia/lymphoma 2-associated X protein (Bax), can induce apoptosis in specific tissues by using tissue specific promoters in silkworm and mosquito. Here, we newly identified a functional promoter in the Asian malaria vector, Anopheles stephensi, which enables gene expression specifically in the testis. We produced a transgenic mosquito line that expresses mouse Bax under the control of this testis-specific promoter. Transgenic mosquito males exhibited aberrant testes without functional sperm and complete sterility, whereas transgenic females maintained normal fecundity. Despite their abnormal testes, the transgenic males maintained normal function of male accessory glands and typical mating behaviour. As a result of mating with these males, females showed refractoriness to further mating. These results suggest that transgenic males induce female sterility via mating. The mosquito is one of the most important disease vectors, and the control of their population benefits global public health. Thus, this Bax-mediated synthetic male-specific sterilization system could be applied to population control of mosquitoes.
机译:条件细胞死亡系统可用于基础科学的各个方面,并具有广泛的应用,包括遗传害虫防治。最近,我们证明了哺乳动物促凋亡因子B细胞白血病/淋巴瘤2相关X蛋白(Bax)的表达可以通过在蚕和蚊子中使用组织特异性启动子来诱导特定组织的凋亡。在这里,我们新发现了亚洲疟疾载体Anopheles stephensi中的一个功能性启动子,该基因可以在睾丸中特异性地表达基因。我们生产了在此睾丸特异性启动子控制下表达小鼠B​​ax的转基因蚊子系。转基因蚊子雄性表现出异常的睾丸,没有精子的功能和完全的不育,而转基因蚊子则保持了正常的繁殖力。尽管睾丸异常,转基因雄性仍保持雄性附属腺正常功能和典型的交配行为。与这些雄性交配的结果是,雌性显示出对进一步交配的耐性。这些结果表明,转基因雄性通过交配诱导雌性不育。蚊子是最重要的疾病媒介之一,控制蚊子的数量有益于全球公共卫生。因此,这种Bax介导的合成雄性特异杀菌系统可用于蚊子的种群控制。

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