title: Genetic control of susceptibility to infection with Plasmodium chabaudi chabaudi AS in inbred mouse strains.
abstract: To identify genetic effects modulating the blood stage replication of the malarial parasite, we phenotyped a group of 25 inbred mouse strains for susceptibility to Plasmodium chabaudi chabaudi AS infection (peak parasitemia, survival). A broad spectrum of responses was observed, with strains such as C57BL/6J being the most resistant (low parasitemia, 100% survival) and strains such as NZW/LacJ and C3HeB/FeJ being extremely susceptible (very high parasitemia and uniform lethality). A number of strains showed intermediate phenotypes and gender-specific effects, suggestive of rich genetic diversity in response to malaria in inbred strains. An F2 progeny was generated from SM/J (susceptible) and C57BL/6J (resistant) parental strains, and was phenotyped for susceptibility to P. chabaudi chabaudi AS. A whole-genome scan in these animals identified the Char1 locus (LOD=7.40) on chromosome 9 as a key regulator of parasite density and pointed to a conserved 0.4-Mb haplotype at Char1 that segregates with susceptibility/resistance to infection. In addition, a second locus was detected in [SM/J × C57BL/6J] F2 mice on the X chromosome (LOD=4.26), which was given the temporary designation Char11. These studies identify a conserved role of Char1 in regulating response to malaria in inbred mouse strains, and provide a prioritized 0.4-Mb interval for the search of positional candidates.
authors: Department of Biochemistry, McGill University, Montreal, Quebec, Canada.
authors: A
authors: A
authors: Laroque
authors: G
authors: G
authors: Min-Oo
authors: M
authors: M
authors: Tam
authors: I
authors: I
authors: Radovanovic
authors: M M
authors: MM
authors: Stevenson
authors: P
authors: P
authors: Gros
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D005260:Female; D020022:Genetic Predisposition to Disease; D006239:Haplotypes; D008288:Malaria / Q000235:genetics*; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D010641:Phenotype; D016788:Plasmodium chabaudi