Natural history and pathophysiology of enterocolitis in the piebald lethal mouse model of Hirschsprung's disease

A breeding colony of piebald lethal mice was established in order to study the natural history of congenital megacolon in a mouse model of Hirschsprung's disease and to investigate mucosal defense mechanisms and secretory functions in enterocolitis complicating congenital megacolon. In experiment 1, 214 mice were studied, 53 of which had congenital megacolon. All piebald lethal mice with congenital megacolon (S1/S1) died at 3 to 11 weeks of age. Two distinct patterns of mortality were identified. A majority of mice (64%) became acutely ill at 3 to 4 weeks of age and died, whereas the remainder died between 9 and 11 weeks of age. The former group of mice exhibited clinical and histologic evidence of severe enterocolitis while the latter group had massive abdominal distension and classical megacolon. In experiment 2, piebald mice with congenital megacolon were killed at the time of acute illness. Significant histologic and immunohistochemical differences were seen in the ganglionic colon between piebald mice with early clinical onset of acute illness and piebald mice with the classical clinical picture of congenital megacolon. In the former group of mice the number of immunocytes in the lamina propria was significantly higher than in control mice (P less than .001), immunoglobulin-producing cells were equally distributed throughout the lamina propria and IgA-containing cells were by far the most abundant cell type identified in the colon. In the latter group of mice, immunocyte responses were significantly low and the distribution of immunocytes markedly different, with the immunoglobulin-producing cells being located only at the deep layer of lamina propria.(ABSTRACT TRUNCATED AT 250 WORDS)