Chapter 13 : Murine Colonic Hyperplasia

Abstract:

Despite the low incidence of clinical cases, transmissible murine colonic hyperplasia is of interest to microbiologists and gastroenterologists alike because of the unusual pathogenesis of the disease. Koch’s postulates have also been fulfilled with Citrobacter freundii biotype 4280, which produces transmissible murine colonic hyperplasia when pure cultures are inoculated into either conventional or germ free mice. The transient hyperplastic state which is induced by C. freundii biotype 4280 has a profound effect on the cytokinetics of the mucosal epithelial cells in the large bowel. These changes also serve to increase the susceptibility of the colonic epithelial cells to the carcinogenic effect of 1,2-dimethylhydrazine (DMH). The cytokinetics of the hyperplastic mucosa in transmissible murine colonic hyperplasia have been characterized by autoradiography of histological sections labeled with [3H]thymidine. The role of eaeA in the pathogenesis of transmissible murine colonic hyperplasia has been examined by the construction of an isogenic mutant of C. freundii biotype 4280. The molecular basis of transmissible murine colonic hyperplasia remains enigmatic. Characteristic histopathological lesions are produced by C. freundii biotype 4280 in the mucosa of the large bowel of laboratory mice prior to the onset of gross hyperplasia. At least one common, indigenous organism has the ability to cause histopathological changes in enterocytes at the site of bacterial adherence which are reminiscent of AE lesions. It seems likely that a better understanding of the molecular pathogenesis of transmissible murine colonic hyperplasia will also bring a better understanding of the role of bacteria in proliferative bowel disease.