Reverse genetics screen identifies six proteins important for malaria development in the mosquito.

Reverse genetics screen identifies six proteins important for malaria development in the mosquito.
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DOI:
10.1111/j.1365-2958.2008.06407.x
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发表时间:
2008-10
影响因子:
3.6
通讯作者:
Sinden RE
Sinden RE
中科院分区:
生物学2区
文献类型:
--
作者:
Ecker A;Bushell ES;Tewari R;Sinden RE

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从脊椎动物宿主到蚊子媒介的传播是疟疾生命周期中的一个主要人口瓶颈,干预战略可以成功地针对这一瓶颈。然而,到目前为止,只有约25寄生虫蛋白表达在这一关键阶段进行了功能分析的基因中断。我们描述了第一个系统的,更大规模的一代和伯氏疟原虫基因敲除(KO)线的表型分析,表征20个基因编码pupillary分泌的蛋白质表达的动合子,寄生虫阶段负责入侵蚊子中肠。在产生的12个KO系中,6个在蚊子发育期间显示寄生虫数量显著减少,导致阻断5个科斯的传播。虽然在三个科斯中肠入侵缺陷,在三个科斯,在孢子形成失败的表达数据,时间点的基本功能和突变体表型相关,突变体表型的母系遗传表明,在动合子形成过程中发生的基本功能,因此在形态异常的几天之前。
Transmission from the vertebrate host to the mosquito vector represents a major population bottleneck in the malaria life cycle that can successfully be targeted by intervention strategies. However, to date only about 25 parasite proteins expressed during this critical phase have been functionally analysed by gene disruption. We describe the first systematic, larger scale generation and phenotypic analysis of Plasmodium berghei knockout (KO) lines, characterizing 20 genes encoding putatively secreted proteins expressed by the ookinete, the parasite stage responsible for invasion of the mosquito midgut. Of 12 KO lines that were generated, six showed significant reductions in parasite numbers during development in the mosquito, resulting in a block in transmission of five KOs. While expression data, time point of essential function and mutant phenotype correlate well in three KOs defective in midgut invasion, in three KOs that fail at sporulation, maternal inheritance of the mutant phenotype suggests that essential function occurs during ookinete formation and thus precedes morphological abnormalities by several days.
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