Mice that are congenic for the char2 locus are susceptible to malaria

Abstract

A major advance has been made towards the positional cloning of char2 (a quantitative trait locus encoding resistance to Plasmodium chabaudi malaria). Mice congenic for the locus have been used to fine map the gene and to prove that char2 plays a significant role in the outcome of malarial infection, independently of other resistance loci.

FIG. 1.

Illustration of the genotype at a selection of microsatellite markers on chromosome 8, inherited by each of the 10 different char2 congenic mouse strains. Congenic line char2-1 is the only line with a C3H/He background genome. All other lines carry a C57BL/6 background genome. The map position (in centimorgans [cM]) of the markers was obtained from the MGI database (http://www.informatics.jax.org/). The map order of the markers, as illustrated here, is based on recombinations observed during breeding of the congenic lines.

FIG. 2.

Outcome of infection in char2 congenic animals and control mice following intravenous injection with 10⁴ P. chabaudi-parasitized red blood cells (RBCs). (A and B) Results of infection of char2-7 congenic animals versus C57BL/6 controls; (C and D) results of infection of char2-1 congenic mice versus C3H/He controls; (E and F) results of infection of char2-11 congenic animals versus C57BL/6 controls. (A, C, and E) Kaplan-Meier cumulative survival plots for congenic mice versus controls. Significant P values (A) are the results of Mantel-Cox analyses of the difference between two curves. Males and females were analyzed separately. (B, D, and F) Plots of the average course of infection for congenic mice versus controls. Significant P values (B) are the results of t tests comparing the peak levels of parasitemia in congenic mice with those in controls. Males and females were considered separately.