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Infection and Immunity, April 2002, p. 2049-2056, Vol. 70, No. 4
0019-9567/02/$04.00+0     DOI: 10.1128/IAI.70.4.2049-2056.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.

Susceptibility to Experimental Cerebral Malaria Induced by Plasmodium berghei ANKA in Inbred Mouse Strains Recently Derived from Wild Stock

S. Bagot,1,2 M. Idrissa Boubou,2 S. Campino,3 C. Behrschmidt,3 O. Gorgette,1 J.-L. Guénet,4 C. Penha-Gonçalves,3 D. Mazier,2 S. Pied,1,2* and P.-A. Cazenave1

Unité d'Immunophysiopathologie Infectieuse, CNRS URA 1961, LEA14C, and Université Pierre et Marie Curie,1 Unité de Génétique des Mammifères, Institut Pasteur, 75724 Paris Cedex 15,4 Unité 511, INSERM, Immunobiologie Cellulaire et Moléculaire des Infections Parasitaires, CHU Pitié-Salpétrière, 75643 Paris Cedex 13, France and,2 Instituto Gulbenkian de Ciencîa, 2780-156 Oeiras, Portugal3

Received 7 September 2001/ Returned for modification 1 November 2001/ Accepted 21 December 2001

The neurological syndrome caused by Plasmodium berghei ANKA in rodents partially mimics the human disease. Several rodent models of cerebral malaria (CM) exist for the study of the mechanisms that cause the disease. However, since common laboratory mouse strains have limited gene pools, the role of their phenotypic variations causing CM is restricted. This constitutes an obstacle for efficient genetic analysis relating to the pathogenesis of malaria. Most common laboratory mouse strains are susceptible to CM, and the same major histocompatibility complex (MHC) haplotype may exhibit different levels of susceptibility. We analyzed the influence of the MHC haplotype on overcoming CM by using MHC congenic mice with C57BL/10 and C3H backgrounds. No correlation was found between MHC molecules and the development of CM. New wild-derived mouse strains with wide genetic polymorphisms were then used to find new models of resistance to CM. Six of the twelve strains tested were resistant to CM. For two of them, F1 progeny and backcrosses performed with the reference strain C57BL/6 showed a high level of heterogeneity in the number and characteristics of the genetic factors associated with resistance to CM.

* Corresponding author. Mailing address: Unité d'Immunophysiopathologie Infectieuse, Institut Pasteur, 25-28 Rue du Dr. Roux, 75724 Paris Cedex 15, France. Phone: 33-1-40-61-84-65. Fax: 33-1-40-61-30-66. E-mail: spied{at}pasteur.fr.

Infection and Immunity, April 2002, p. 2049-2056, Vol. 70, No. 4
0019-9567/02/$04.00+0     DOI: 10.1128/IAI.70.4.2049-2056.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.



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