Marrelli Mauro T, Li Chaoyang, Rasgon Jason L, Jacobs-Lorena Marcelo
Department of Molecular Microbiology and Immunology, Bloomberg School of Public Health and Malaria Research Institute, The Johns Hopkins University, Baltimore, MD 21205, USA.
Proc Natl Acad Sci U S A. 2007 Mar 27;104(13):5580-3. doi: 10.1073/pnas.0609809104. Epub 2007 Mar 19.
The introduction of genes that impair Plasmodium development into mosquito populations is a strategy being considered for malaria control. The effect of the transgene on mosquito fitness is a crucial parameter influencing the success of this approach. We have previously shown that anopheline mosquitoes expressing the SM1 peptide in the midgut lumen are impaired for transmission of Plasmodium berghei. Moreover, the transgenic mosquitoes had no noticeable fitness load compared with nontransgenic mosquitoes when fed on noninfected mice. Here we show that when fed on mice infected with P. berghei, these transgenic mosquitoes are more fit (higher fecundity and lower mortality) than sibling nontransgenic mosquitoes. In cage experiments, transgenic mosquitoes gradually replaced nontransgenics when mosquitoes were maintained on mice infected with gametocyte-producing parasites (strain ANKA 2.34) but not when maintained on mice infected with gametocyte-deficient parasites (strain ANKA 2.33). These findings suggest that when feeding on Plasmodium-infected blood, transgenic malaria-resistant mosquitoes have a selective advantage over nontransgenic mosquitoes. This fitness advantage has important implications for devising malaria control strategies by means of genetic modification of mosquitoes.
将损害疟原虫在蚊子种群中发育的基因引入，是一种正在被考虑用于疟疾控制的策略。转基因对蚊子适应性的影响是影响该方法成功与否的关键参数。我们之前已经表明，在中肠腔中表达SM1肽的按蚊传播伯氏疟原虫的能力受损。此外，与以未感染小鼠为食的非转基因蚊子相比，转基因蚊子没有明显的适应性负担。在此我们表明，当以感染了伯氏疟原虫的小鼠为食时，这些转基因蚊子比同胞非转基因蚊子更具适应性（繁殖力更高且死亡率更低）。在笼子实验中，当蚊子以感染了产生配子体的寄生虫（ANKA 2.34株）的小鼠为食时，转基因蚊子逐渐取代了非转基因蚊子，但当以感染了缺乏配子体的寄生虫（ANKA 2.33株）的小鼠为食时则没有。这些发现表明，当以感染疟原虫的血液为食时，转基因抗疟蚊子比非转基因蚊子具有选择性优势。这种适应性优势对于通过对蚊子进行基因改造来制定疟疾控制策略具有重要意义。
