International Mammalian Genome Society

The 16th International Mouse Genome Conference (2002)


P Denny
MRC UK Mouse Genome Centre & Mammalian Genetics Unit.

1) Hopes E, 2) Gingles N, 3) Broman KW, 4) Morten J, 5) McPheat W, 2) Alexander J, 2) Andrew PW, 1) Brown SDM
1) MRC Mammalian Genetics Unit, 2) University of Leicester, 3) Johns Hopkins University, 4) Research and Development Genetics AstraZeneca, 5) Cell Biology and Biochemistry AstraZeneca

Streptococcus pneumoniae is responsible for the majority of cases of community-acquired pneumonia and is also a significant cause of meningitis, bacteremia and otitis media in children.  Antibiotic drugs are the standard therapy and vaccination offers protection against a spectrum of pneumococcal serotypes, but horizontal gene transfer may ultimately negate the effectiveness of both vaccines and antibiotics.  It is clear that a better understanding of the host response to this bacterium is essential for improved preventative and therapeutic treatments.  There is a significant genetic contribution to host susceptibility to pneumococcal infection, but the limited numbers of case-confirmed pedigrees or sibling pairs preclude linkage analysis.  We have therefore developed a genetic model using inbred mouse strains that exhibit differences in susceptibility to pneumococcal infection.BALB/c and CBA/Ca are resistant and susceptible to infection by S. pneumoniae, respectively.  We followed two traits in the progeny of a (BALB/c x CBA/Ca)F1 intercross; survival time and the level of circulating bacteria.  A complex phenotypic distribution was seen in the F2 generation, with many animals surviving the full length of the experiment and others succumbing to infection early on, in a way similar to the CBA/Ca parent.  Many F2 animals also failed to develop significant bacteremia, but there was not an absolute correlation between bacteremia level and survival.  We will present details of the phenotypes and the mapping of a major QTL conferring susceptibility to infection.

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