Only recently has it become well documented that Crohn's disease and ulcerative colitis have a genetic cause. Similarly, certain inbred strains of mice such as C3H/HeJ have an increased incidence of spontaneous inflammatory bowel disease and are also more susceptible to experimentally-induced colitis. By selectively inbreeding C3H/HeJ mice with clinical signs of inflammatory bowel disease (IBD), we established a pedigreed substrain, C3H/HeJBir, with a relatively high incidence of a form of murine IBD. In addition, C3H/HeJBir mice are highly susceptible to experimental murine colitis induced by dextran sulfate sodium (DSS). Our long term objective is to determine the chromosomal location of genes that increase susceptibility of C3H/HeJBir and other strains of mice to IBD. We will use recombinant inbred strains and genetic crosses between C3H/HeJBir mice and DSS resistant strains to map the genes that modify the severity and histopathology of DSS experimental colitis. The results will predict the location of homologous genes in man and may also identify candidate IBD susceptibility genes in both species. Even if the primary genetic defects in human IBD are located elsewhere in the genome, it is still possible that the homologous regions identified by mouse genetics will contain modifier genes important in determining penetrance, identifying prognostic indicators, or developing various modes of therapy for human disease.
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