Genetic control of parasite clearance leads to resistance to Plasmodium berghei ANKA infection and confers immunity.
Unprecedented cure after infection with the lethal Plasmodium berghei ANKA was observed in an F2 progeny generated by intercrossing the wild-derived WLA and the laboratory C57BL/6 mouse strains. Resistant mice were able to clear parasitaemia and establish immunity. The observed resistance was disclosed as a combinatorial effect of genetic factors derived from the two parental strains. Genetic mapping of survival time showed that the WLA allele at a locus on chromosome 1 (colocalizing with Berghei resistance 1 (Berr1), a locus associated with resistance to experimental cerebral malaria) increases the probability to resist early death. Also, the C57Bl/6 allele at a novel locus on chromosome 9 (Berr3) confers overall resistance to this lethal Plasmodium infection. This report underlines the value of using wild-derived mouse strains to identify novel genetic factors in the aetiology of disease phenotypes, and provides a unique model for studying parasite clearance and immunity associated with malaria.
Instituto Gulbenkian de Ciência, Oeiras, Portugal.
S
S
Campino
S
S
Bagot
M-L
ML
Bergman
P
P
Almeida
N
N
Sepúlveda
S
S
Pied
C
C
Penha-Gonçalves
D
D
Holmberg
P-A
PA
Cazenave
D000818:Animals; D002874:Chromosome Mapping; D002875:Chromosomes / Q000235:genetics*; D020022:Genetic Predisposition to Disease / Q000235:genetics; D007113:Immunity, Innate / Q000235:genetics*; D008288:Malaria / Q000235:genetics* / Q000276:immunology / Q000469:parasitology; D051379:Mice; D010962:Plasmodium berghei / Q000276:immunology; D040641:Quantitative Trait Loci / Q000235:genetics* / Q000276:immunology