MDR1A (ABCB1) DEFICIENT CF-1 MUTANT MICE IS SUSCEPTIBLE TO CEREBRAL MALARIA INDUCED BY PLASMODIUM BE
June 27th, 2008 | by admin |MDR1A (ABCB1) DEFICIENT CF-1 MUTANT MICE IS SUSCEPTIBLE TO CEREBRAL MALARIA INDUCED BY PLASMODIUM BERGHEI ANKA.
Under experimental conditions, P. berghei infection causes cerebral malaria (CM) in susceptible strains of mice such as C57BL/6 and CBA/Ca, while BALB/c or DBA/2J strains serve as a model for CM-resistant mice. The aim of this study was to investigate the susceptibility of the CF1 mouse strain, carrying a spontaneous mutation of the mdr1a gene, to an infection with Plasmodium berghei ANKA (PbA). The Mdr1a gene codes for P-glycoprotein (P-gp/ABCB1), an efflux pump which is one of the major components of the blood-brain barrier. P-gp extrudes a broad range of xenobiotics from the brain to blood, preventing accumulation and toxicity in the central nervous system. CF1 mdr1a (-/-) mice are used to investigate drug transport by efflux pumps. As many antimalarial agents are effluxed by P-gp (mefloquine, quinine), it was important to investigate if CF1 mice can develop cerebral malaria in order 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.
Barraud de Lagerie S, Fernandez C, German-Fattal M, Gantier JC, Gimenez F, Farinotti R.