MDR1A (ABCB1)-deficient CF-1 mutant mice are susceptible to cerebral malaria induced by Plasmodium berghei ANKA.
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.
de Lagerie
Sylvie Barraud
SB
Clinical Pharmacy Unit EA 2706, University of Paris Sud 11, 5 rue JB Clement, Chatenay-Malabry, 92296, France. sylvie.vilatte@psl.aphp.fr
Fernandez
Christine
C
German-Fattal
Michèle
M
Gantier
Jean-Charles
JC
Gimenez
François
F
Farinotti
Robert
R
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
D018435:ATP Binding Cassette Transporter, Subfamily B; D006420:Hemeproteins; C020753:hemozoin; C095122:multidrug resistance protein 3