Methoprene, a juvenile hormone (JH) analog, is widely used for insect control, but its mode of action is not known. To study methoprene action in the yellow fever mosquito, Aedes aegypti, the E93 (ecdysone-induced transcription factor) was knocked out using the CRISPR-Cas9 system. The E93 mutant pupae retained larval tissues similar to methoprene-treated insects. These insects completed pupal ecdysis and died as pupa. In addition, the expression of transcription factors, broad complex and Krüppel homolog 1 (Kr-h1), increased and that of programmed cell death (PCD) and autophagy genes decreased in E93 mutants. These data suggest that methoprene functions through JH receptor, methoprene-tolerant, and induces the expression of Kr-h1, which suppresses the expression of E93, resulting in a block in PCD and autophagy of larval tissues. Failure in the elimination of larval tissues and the formation of adult structures results in their death. These results answered long-standing questions on the mode of action of methoprene.

中文翻译：

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CRISPR-Cas9 基因组编辑揭示了甲氧普林在黄热病蚊子、埃及伊蚊中的作用模式

甲氧普林是一种保幼激素 (JH) 类似物，广泛用于昆虫防治，但其作用方式尚不清楚。为了研究甲氧普林在黄热病蚊子埃及伊蚊中的作用，使用 CRISPR-Cas9 系统敲除了E93 （蜕皮激素诱导的转录因子）。E93 突变体蛹保留了类似于甲氧普林处理过的昆虫的幼虫组织。这些昆虫完成蛹蜕皮并作为蛹死亡。此外，E93中转录因子、广泛复合物和Krüppel 同系物 1 ( Kr-h1 ) 的表达增加，程序性细胞死亡 (PCD) 和自噬基因的表达减少突变体。这些数据表明，甲氧普林通过 JH 受体发挥作用，对甲氧普林具有耐受性，并诱导Kr-h1的表达，从而抑制E93的表达，从而阻断 PCD 和幼虫组织的自噬。幼虫组织的消除和成体结构的形成失败导致它们死亡。这些结果回答了长期存在的关于甲氧普林作用方式的问题。