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

A synthetic male-specific sterilization system using the mammalian pro-apoptotic factor in a malaria vector mosquito
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DOI:
10.1038/s41598-019-44480-0
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发表时间:
2019-06
期刊:
影响因子:
4.6
通讯作者:
D. Yamamoto;M. Sumitani;K. Kasashima;H. Sezutsu;H. Matsuoka;H. Kato
D. Yamamoto;M. Sumitani;K. Kasashima;H. Sezutsu;H. Matsuoka;H. Kato
中科院分区:
综合性期刊3区
文献类型:
--
作者:
D. Yamamoto;M. Sumitani;K. Kasashima;H. Sezutsu;H. Matsuoka;H. Kato

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条件细胞死亡系统可用于基础科学的各个方面,具有广泛的应用,包括遗传害虫控制。我们最近证明,通过在家蚕和蚊子中使用组织特异性启动子,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) 的表达可以诱导特定组织中的细胞凋亡。在这里,我们在亚洲疟疾载体史氏按蚊中新发现了一个功能启动子,它能够在睾丸中特异性表达基因。我们生产了一种转基因蚊子系,该系在该睾丸特异性启动子的控制下表达小鼠 Bax。转基因雄性蚊子表现出异常的睾丸,没有功能性精子和完全不育,而转基因雌性蚊子则保持正常的生育能力。尽管睾丸异常,转基因雄性仍保持雄性附属腺的正常功能和典型的交配行为。由于与这些雄性交配,雌性表现出不愿进一步交配。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,控制其数量有利于全球公共卫生。因此,这种 Bax 介导的合成雄性特异性绝育系统可以应用于蚊子的种群控制。
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.