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Genetic control of susceptibility to infection with Plasmodium chabaudi chabaudi AS in inbred mouse strains

Genes & Immunity volume 13, pages 155–163 (2012)Cite this article

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.

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Acknowledgements

We thank Dr Molly Bogue, Director of the mouse Phenome Project at the Jackson Laboratory, for providing mice and Dr Gary Churchill at the Jackson Laboratory for sharing a list of 28 000 SNPs from Chr. 9. We also thank Dr Tamio Ohno at Nagoya University for providing DNA from NC/Jic mice, and further acknowledge Susan Gauthier for breeding and maintaining the mice. This work was supported by a CIHR Team Grant in Malaria (CTP 79842) and operating grant MOP-79343 (PG), FRSQ (AL) and CIHR (GM-O, AL) studentships.

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Authors and Affiliations

  1. Department of Biochemistry, McGill University, Montreal, Quebec, Canada

    A Laroque, G Min-Oo, I Radovanovic & P Gros

  2. Montreal General Hospital Research Institute, Montreal, Quebec, Canada

    M Tam & M M Stevenson

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  1. A Laroque
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Correspondence to P Gros.

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Laroque, A., Min-Oo, G., Tam, M. et al. Genetic control of susceptibility to infection with Plasmodium chabaudi chabaudi AS in inbred mouse strains. Genes Immun 13, 155–163 (2012). https://doi.org/10.1038/gene.2011.67

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