1. Disruption of a Plasmodium falciparum gene linked to male sexual development causes early arrest in gametocytogenesis
- Author
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Furuya, Tetsuya, Mu, Jianbing, Hayton, Karen, Liu, Anna, Duan, Junhui, Nkrumah, Louis, Joy, Deirdre A., Fidock, David A., Fujioka, Hisashi, Vaidya, Akhil B., Wellems, Thomas E., and Su, Xin-zhuan
- Subjects
Chromosome mapping -- Research ,Gametocytes -- Research ,Malaria -- Research ,Plasmodium falciparum -- Research ,Plasmodium falciparum -- Physiological aspects ,Science and technology - Abstract
A male gametocyte defect in the Plasmodium falciparum Dd2 parasite was previously discovered through the observation that all progeny clones in a Dd2 x HB3 genetic cross were the result of fertilization events between Dd2 female and HB3 male gametes. A determinant linked to the defect in Dd2 was subsequently mapped to an 800-kb segment on chromosome 12. Here, we report further mapping of the determinant to an 82-kb region and the identification of a candidate gene, P. falciparurn male development gene 1 (pfmdv-1), that is expressed at a lower level in Dd2 compared with the wild-type normal male gametocyte-producing ancestor W2. Pfmdv-1 protein is sexual-stage specific and is located on the gametocyte plasma membrane, parasitophorous vacuole membrane, and the membranes of cleft-like structures within the erythrocyte. Disruption of pfmdv-1 results in a dramatic reduction in mature gametocytes, especially functional male gametocytes, with the majority of sexually committed parasites developmentally arrested at stage I. The pfmdv-1-knockout parasites show disturbed membrane structures, particularly multimembrane vesicles/tubes that likely derive from deformed cleft-like structures. Mosquito infectivity of the knockout parasites was also greatly reduced but not completely lost. The results suggest that pfmdv-1 plays a key role in gametocyte membrane formation and integrity. gametocyte | genetic mapping | malaria | microarray
- Published
- 2005