International Mammalian Genome Society

The 16th International Mouse Genome Conference (2002)


J Böse
German Research Center for Biotechnology (GBF)

2) Medina E, 2) Goldmann O, 2) Chhatwal GS, 1,2) Lengeling A
1) Junior Research Group Infection Genetics, 2) Department of Microbial Pathogenesis and Vaccine ResearchDivision of Microbiology, German Research Center for Biotechnology (GBF)

Streptococcus pyogenes (Group A streptococcus, GAS) is an important bacterial Gram-positive extracellular pathogen, which can cause a variety of clinical manifestations in humans. By infecting different inbred strains of mice with S. pyogenes we observed that resistance/susceptibility to GAS infections is genetically determined. BALB/cJ, C57BL/10J and DBA/2J mice were found to be the most resistant strains able to clear and survive the infection. In contrast, C3H/HeN, A/J and CBA/J mice were much more susceptible, and their inability to control bacterial growth resulted in bacteremia and death. In addition, susceptibility to S. pyogenes infection was influenced by sex, with males being more susceptible than females.A genetic linkage study was initiated to investigate the observed differences to S. pyogenes infection. We used BALB/c and C3H/HeN  mice in a backcross mapping experiment and infected the female F2R-progeny with S. pyogenes. These animals were monitored for survival time and bacterial blood counts post infection, respectively. In a genome wide screen we identified a QTL on chromosome 7 controlling resistance to S. pyogenes at a suggestive linkage level. Further QTLs showing as yet non-significant linkage were detected on chromosomes 1, 2 and 17. Currently, we are analysing more backcross animals to increase the statistical significance of our linkage analysis.The identification and characterization of relevant loci/genes accounting for resistance or susceptibility of mice to S. pyogenes infection by fine mapping, linkage analysis and candidate approaches, respectively, will help to characterize the molecular mechanisms involved in the pathogenesis of these infections in humans.

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