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Genetic analysis of susceptibility to Chlamydia trachomatis in mouse

Genes & Immunity volume 7, pages 122–129 (2006)Cite this article

Abstract

Chlamydia trachomatis is a bacterial pathogen that is a major cause of blindness and infertility in diverse populations across the world. In an effort to model genetic complexities that are observed in human populations and to identify novel genes involved in susceptibility to C. trachomatis, we have adapted a murine model of systemic infection for use in genetic analysis. In this model, chlamydial colonization and replication is measured in the spleens of mice shortly after intravenous delivery of C. trachomatis L2. Here, we show that C57BL/6J and C3H/HeJ inbred mice are differentially susceptible to this systemic infection. Additionally, fibroblasts cultured from C57BL/6J and C3H/HeJ embryos are differentially permissive for chlamydial replication. We have taken advantage of this natural variation to map quantitative trait loci on Chromosomes 2, 3, and 11 that segregate with the bacterial load in F2 cross progeny during the acute phase of C. trachomatis infection in vivo. To validate our mapping results, we also generated mice that are congenic for a portion of Chromosome 11 from the susceptible parent. This congenic interval confers increased susceptibility to C. trachomatis, both in vivo and in vitro, suggesting that our screen identified at least one gene that is involved in cellular resistance to C. trachomatis replication.

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Acknowledgements

We thank Nathan Billings, James Nicholas Lafave, David Regan, and Tao Zou for technical support. Thanks also to Russell Vance for critical reading of the manuscript. This work was supported by an Investigator grant to WFD by Howard Hughes Medical Institute, and by National Institutes of Health Grants AI039558 and AI055900 to MNS. JC was supported by a research fellowship from the Deutsche Forschungsgemeinschaft. IBH was supported by a predoctoral research fellowship from the National Science Foundation.

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Authors and Affiliations

  1. Department of Genetics, Harvard Medical School, Boston, MA, USA

    I Bernstein-Hanley, J Coers & W F Dietrich

  2. Department of Microbiology and Molecular Genetics, Harvard Medical School, Boston, MA, USA

    Z R Balsara & M N Starnbach

  3. Biopolymers Facility, Harvard Medical School, Boston, MA, USA

    W Ulmer

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  1. I Bernstein-Hanley
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  2. Z R Balsara
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  3. W Ulmer
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  4. J Coers
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  5. M N Starnbach
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  6. W F Dietrich
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Correspondence to W F Dietrich.

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Bernstein-Hanley, I., Balsara, Z., Ulmer, W. et al. Genetic analysis of susceptibility to Chlamydia trachomatis in mouse. Genes Immun 7, 122–129 (2006). https://doi.org/10.1038/sj.gene.6364285

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