title: MDR1A (ABCB1)-deficient CF-1 mutant mice are susceptible to cerebral malaria induced by Plasmodium berghei ANKA.
abstract: Under experimental conditions, Plasmodium berghei infection causes cerebral malaria (CM) in susceptible strains of mice such as C57BL/6 and CBA/Ca, whereas BALB/c or DBA/2J strains serve as a model for CM-resistant mice. The aim of the present study was to investigate the susceptibility of the CF1 mouse strain, carrying a spontaneous mutation of the mdr1a gene, to infection with Plasmodium berghei ANKA (PbA). The mdr1a gene codes for P-glycoprotein (P-gp/ABCB1), an efflux pump that is one of the major components of the blood-brain barrier. P-gp effluxes a broad range of xenobiotics from the brain to blood, preventing accumulation and toxicity in the central nervous system. CFI mdr1a (-/-) mice are used to investigate drug transport by efflux pumps. Because many antimalarial agents are effluxed by P-gp (mefloquine, quinine), it was important to determine whether CF1 mice can develop cerebral malaria to predict drug toxicity during cerebral malaria. Our work showed that CF1 mdr1a (-/-) mice are susceptible to PbA. CF1 and C57BL/6N mice (the reference strain) infected with PbA have similar profiles with regard to clinical signs, brain histological lesions, and brain macrophagic activation observed by immunohistological methods.
authors.affiliation: Clinical Pharmacy Unit EA 2706, University of Paris Sud 11, 5 rue JB Clement, Chatenay-Malabry, 92296, France. sylvie.vilatte@psl.aphp.fr
authors.forename: Sylvie Barraud
authors.initials: SB
authors.lastname: de Lagerie
authors.forename: Christine
authors.initials: C
authors.lastname: Fernandez
authors.forename: Michèle
authors.initials: M
authors.lastname: German-Fattal
authors.forename: Jean-Charles
authors.initials: JC
authors.lastname: Gantier
authors.forename: François
authors.initials: F
authors.lastname: Gimenez
authors.forename: Robert
authors.initials: R
authors.lastname: Farinotti
mesh_terms: D018435:ATP Binding Cassette Transporter, Subfamily B / Q000235:genetics* / Q000502:physiology; D000818:Animals; D001921:Brain / Q000473:pathology; D004195:Disease Models, Animal; D004198:Disease Susceptibility; D005260:Female; D019084:Fluorescent Antibody Technique, Indirect; D006420:Hemeproteins / Q000032:analysis; D016779:Malaria, Cerebral / Q000235:genetics / Q000276:immunology* / Q000469:parasitology; D051379:Mice; D008810:Mice, Inbred C57BL; D008817:Mice, Mutant Strains; D017628:Microglia / Q000473:pathology; D010962:Plasmodium berghei / Q000276:immunology* / Q000472:pathogenicity
chemical_list: D018435:ATP Binding Cassette Transporter, Subfamily B; D006420:Hemeproteins; C020753:hemozoin; C095122:multidrug resistance protein 3