title: Driving midgut-specific expression and secretion of a foreign protein in transgenic mosquitoes with AgAper1 regulatory elements.
abstract: The Anopheles gambiae adult peritrophic matrix protein 1 (AgAper1) regulatory elements were used to drive the expression of phospholipase A2 (PLA2), a protein known to disrupt malaria parasite development in mosquitoes. These AgAper1 regulatory elements were sufficient to promote the accumulation of PLA2 in midgut epithelial cells before a blood meal and its release into the lumen upon blood ingestion. Plasmodium berghei oocyst formation was reduced by approximately 80% (74-91% range) in transgenic mosquitoes. Blood-seeking behaviour and survival of AgAper1-PLA2 transgenic mosquitoes were comparable to sibling wild-type mosquitoes, while fertility was substantially lower. Ultrastructural studies suggest that decreased fitness is a consequence of internal damage to midgut epithelial cells.
authors.affiliation: Department of Molecular Microbiology and Immunology, John Hopkins Bloomberg School of Public Health, Malaria Research Institute, Baltimore, MD 21205, USA.
authors.forename: E G
authors.initials: EG
authors.lastname: Abraham
authors.forename: M
authors.initials: M
authors.lastname: Donnelly-Doman
authors.forename: H
authors.initials: H
authors.lastname: Fujioka
authors.forename: A
authors.initials: A
authors.lastname: Ghosh
authors.forename: L
authors.initials: L
authors.lastname: Moreira
authors.forename: M
authors.initials: M
authors.lastname: Jacobs-Lorena
mesh_terms: D000818:Animals; D030801:Animals, Genetically Modified / Q000235:genetics / Q000378:metabolism*; D000852:Anopheles / Q000235:genetics* / Q000378:metabolism*; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism*; D004064:Digestive System / Q000378:metabolism / Q000648:ultrastructure; D005247:Feeding Behavior; D005260:Female; D005298:Fertility / Q000235:genetics; D019476:Insect Proteins / Q000235:genetics / Q000378:metabolism*; D008297:Male; D011401:Promoter Regions, Genetic; D012045:Regulatory Sequences, Nucleic Acid
chemical_list: C113435:Aper1 protein, Anopheles gambiae; D002352:Carrier Proteins; D019476:Insect Proteins