Mapping of the Plasmodium chabaudi resistance locus char2

Abstract

Animals congenic for the char2 host response locus to the murine malarial parasite Plasmodium chabaudi have been bred, and they demonstrated a phenotypic difference from the parental lines. These congenic lines have been crossed back to the parental line to generate recombinants across the congenic intervals. The recombinants were inbred, and the subcongenic intervals were fixed. These lines were then challenged with parasites and assessed as being either resistant or susceptible. From the analysis of many subcongenic lines, it has become obvious that there are at least two loci underlying the char2 locus and that both of these mediate resistance when the haplotype derives from the resistant C57BL/6 strain.

FIG. 1.

Genotype of the original panel of char2 congenic strains at a selection of microsatellite markers on chromosome 8. These lines have C57BL/6 background genomes and C3H/He congenic intervals. Map positions (in centimorgans [cM]) were obtained from the Massachusetts Institute of Technology database (http://www.broad.mit.edu/resources.html).

FIG. 2.

Genotype of the recombinant strains derived from the Char2-7 congenic line at a selection of microsatellite markers on chromosome 8. Map positions (in centimorgans [cM]) were obtained from the Massachusetts Institute of Technology database.

FIG. 3.

Mortality rates for Char2-7 recombinant congenic and C57BL/6 parental mice following infection with P. chabaudi pRBCs. Data are means ± SEM.

FIG. 4.

Course and outcome of infection in Char2-7, Char2-8, and Char2-11 congenic mice and C57BL/6 controls. A. Mortality rates in the years 2000 to 2001 and 2003 to 2004. B. Kaplan-Meier cumulative survival curve from a 2003 to 2004 challenge. C. Average blood-stage parasitemia over the course of infection from a 2003 to 2004 challenge. Data are presented as means ± SEM.

FIG. 5.

Effect of normalization on mortality rates for each congenic strain. Standard deviations are also shown.