International Mammalian Genome Society

logo18th International Mouse Genome Conference

17-22 October 2004, Seattle, USA


ORAL PRESENTATION

THURSDAY OCTOBER 21

9.30am – 9.45am

MECHANISM OF RESISTANCE TO PLASMODIUM CHABAUDI IN MICE IS MEDIATED THROUGH THE RED CELL AND A TOTALLY SYNERGISTIC NON-ERYTHROCYTIC PATHWAY

Lin E, Marshall V, Burt RA, Foote SJ

The Walter & Eliza Hall Institute, Parkville, Australia

P. chabaudi infection in mice is a model for the severe anaemia seen in falciparum infections. Inbred mice strains are differentially susceptible to malaria. We have mapped three loci involved in outcome to this infection and have generated mice reciprocally congenic for these loci on several strains of mouse. These congenic animals have phenotypes different from their wildtype parents. Parasitaemias are more informative than clinical outcome in differentiating between the congenic animals. In one case, a congenic animal carrying a locus predicted to encode susceptibility was much more resistant than even the “resistant” animal. Analysis of the ability of red cells from congenic mice to sustain the growth of the parasite has been compared to wildtype using a novel comparative in vivo parasite survival assay. Mice congenic for the lmr2 locus demonstrate a curious effect where the origin of the animal receiving the red cells modulates the effect of the red cells. This means that a red cell factor interacts with another, non-red cell factor in a completely synergistic fashion. Other haematological parameters also implicate the origin of the red cell in susceptibility to disease. Another congenic, for the char3 region on chromosome 17 displays a more resistant phenotype, despite the donor region coming from a susceptible animal. This line produces more lymphocytes at around the time of peak parasitaemia. These are interesting cells expressing cell surface markers from B, T and macrophage cell lineages.

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