title: Disruption of a Plasmodium falciparum gene linked to male sexual development causes early arrest in gametocytogenesis.
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. falciparum 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.
authors.affiliation: Laboratory of Malaria and Vector Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892-8132, USA.
authors.forename: Tetsuya
authors.initials: T
authors.lastname: Furuya
authors.forename: Jianbing
authors.initials: J
authors.lastname: Mu
authors.forename: Karen
authors.initials: K
authors.lastname: Hayton
authors.forename: Anna
authors.initials: A
authors.lastname: Liu
authors.forename: Junhui
authors.initials: J
authors.lastname: Duan
authors.forename: Louis
authors.initials: L
authors.lastname: Nkrumah
authors.forename: Deirdre A
authors.initials: DA
authors.lastname: Joy
authors.forename: David A
authors.initials: DA
authors.lastname: Fidock
authors.forename: Hisashi
authors.initials: H
authors.lastname: Fujioka
authors.forename: Akhil B
authors.initials: AB
authors.lastname: Vaidya
authors.forename: Thomas E
authors.initials: TE
authors.lastname: Wellems
authors.forename: Xin-zhuan
authors.initials: XZ
authors.lastname: Su
mesh_terms: D000818:Animals; D003593:Cytoplasm / Q000378:metabolism; D015536:Down-Regulation; D004912:Erythrocytes / Q000469:parasitology; D017125:Genes, Protozoan; D005854:Germ Cells / Q000166:cytology*; D010963:Plasmodium falciparum / Q000235:genetics* / Q000254:growth & development*; D020133:Reverse Transcriptase Polymerase Chain Reaction