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利用 CRISPR 靶向的雄性不育突变来抑制 的雌性育性。

Suppression of female fertility in with a CRISPR-targeted male-sterile mutation.

机构信息

Department of Molecular, Cellular, and Developmental Biology, University of California, Santa Barbara, CA 93106.

Neuroscience Research Institute, University of California, Santa Barbara, CA 93106.

出版信息

Proc Natl Acad Sci U S A. 2021 Jun 1;118(22). doi: 10.1073/pnas.2105075118.

Abstract

spread devastating viruses such as dengue, which causes disease among 100 to 400 million people annually. A potential approach to control mosquito disease vectors is the sterile insect technique (SIT). The strategy involves repeated release of large numbers of sterile males, which reduces insect populations because the sterile males mate and thereby suppress the fertility of females that would otherwise mate with fertile males. While SIT has been successful in suppressing certain agricultural pests, it has been less effective in depressing populations of This limitation is in part because of the fitness effects resulting from mutagenizing the mosquitoes nonspecifically. Here, we introduced and characterized the impact on female fertility of an mutation that disrupts a gene that is specifically expressed in testes. We used CRISPR/Cas9 to generate a null mutation in the () gene, which eliminates male fertility. When we allowed wild-type females to first mate with mutant males, most of the females did not produce progeny even after being subsequently exposed to wild-type males. We also introduced mutant and wild-type males simultaneously with wild-type females and found that a larger number of mutant males relative to the wild-type males was effective in significantly suppressing female fertility. These results raise the possibility of employing sterile males to improve the efficacy of SIT in suppressing populations of through repeated releases and thereby reduce the transmission of viruses by these invasive mosquitoes.

摘要

传播诸如登革热等毁灭性病毒,每年导致 1 亿至 4 亿人患病。控制蚊虫病媒的一种潜在方法是利用不育昆虫技术(SIT)。该策略涉及反复释放大量不育雄虫,由于不育雄虫交配并因此抑制与可育雄虫交配的雌虫的生育能力,从而减少昆虫种群。尽管 SIT 在抑制某些农业害虫方面取得了成功,但在抑制这种害虫方面效果较差。这种局限性部分是由于非特异性诱变蚊子导致的适应度效应。在这里,我们引入并描述了一种破坏专门在睾丸中表达的基因的突变对雌性生育能力的影响。我们使用 CRISPR/Cas9 在 ()基因中产生了一个无效突变,从而消除了雄性生育能力。当我们允许野生型雌性首先与突变雄性交配时,大多数雌性即使随后暴露于野生型雄性也无法产生后代。我们还同时引入突变型和野生型雄性与野生型雌性交配,发现与野生型雄性相比,更多的突变型雄性能够有效地显著抑制雌性生育能力。这些结果提出了利用不育雄性来提高 SIT 抑制种群的功效的可能性,通过反复释放来减少这些入侵蚊子传播病毒的可能性。

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