Abstract
A mouse model was used to study the genetic control of differential host response to pulmonary infection with Chlamydia pneumoniae. The A/J and C57BL/6 strains show differential response to intranasal infection with respect to their ability to clear pulmonary bacterial load and the extent of lung pathology developed by 2 weeks post infection. The genetic basis of this interstrain difference was studied by whole-genome scan in an informative [A/J × C57BL/6J] F2 cross using the pulmonary microbial load as a phenotypic readout of host response. We detected a highly significant linkage (LOD score=11.5) on chromosome 17 that overlaps with the major histocompatibility (MHC) locus. This quantitative trait locus (QTL) accounts for ∼30% of the phenotypic variance with B6 alleles conferring susceptibility and inherited in a recessive fashion. Significant linkage was also detected to chromosome 5 in female mice, while chromosome 6 showed suggestive linkage in male mice, pointing to additional complexity in the genetic control of the difference in susceptibility observed in A/J and C57BL/6J.
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Acknowledgements
We thank Susan Gauthier for assistance with the breeding of the mice. This work was supported by NIH Public Health Service RO1 Grant AI47202 to BK. GM is supported by a CIHR Canada Graduate Scholarship, and PG is supported by a James McGill Professorship. The authors have no competing financial interests.
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Min-Oo, G., Lindqvist, L., Vaglenov, A. et al. Genetic control of susceptibility to pulmonary infection with Chlamydia pneumoniae in the mouse. Genes Immun 9, 383–388 (2008). https://doi.org/10.1038/sj.gene.6364450
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DOI: https://doi.org/10.1038/sj.gene.6364450
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