International Mammalian Genome Society

17th International Mouse Genome Conference

9-12 November 2003, Braunschweig, Germany


POSTER 201 - GENETIC ANALYSIS OF HOST SUSEPTIBILITY TO CARDIOVIRULENT COXSACKIE VIRUS B3 INFECTION

Aly M
University of Ottawa

Co-Authors: Vidal S
Institutions: University of Ottawa

Coxsackie virus B3 (CVB3) is responsible of 50% of viral myocarditis cases in North America. Differences in disease severity caused by a given strain of CVB3 are thought to be largely related to host genetic factors, for which little is known. Infection of mice with CVB3 mimic human heterotypic responses providing a useful model to identify the host genetic determinants of viral myocarditis. To identify those genes and further understand the molecular mechanisms of the disease progression we are taking advantage of naturally occurring variability among inbred strains for the genetic analysis of three CVB3 induced phenotypes: viral load in target organs, weight loss percentage and heart histopathology. A new modified Triangle background algorithm was developed to quantify heart histopathology from florescent damaged cardiomyocytes images. An F2 intercross was constructed using inbred A and B10.A mice as progenitors, which display resistance and sensitivity, respectively, to CVB3-induced myocarditis. Our statistical analysis for weight loss percentage and heart histopathology indicated that the Pearson's correlation coefficient for these traits is highly significant. In the F2 segregating population, we observed a normal distribution of CVB3-induced phenotypes characteristic of complex genetic control. Preliminary genetic analysis excluded a contribution of the Natural Killer gene complex, on distal chromosome 6, to the variability in CVB3-susceptibility. Future studies will involve a genome scan approach to identify genomic locations containing genes underlying differences in host response mechanisms to infection.


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