title: Can colonic migrating motor complexes occur in mice lacking the endothelin-3 gene?
abstract: In mammals, colonic migrating motor complexes (CMMC) are a major propulsive contraction responsible for the expulsion of faecal content. Mice with a mutation of the endothelin-3 gene raised on a 129SL background strain have ~70% colonic aganglionosis, lack CMMC, and are lethal within 12 days postpartum. In contrast, endothelin-3 mutant mice raised and maintained on a C57BL6 background strain (lethal-spotted (ls/ls) mice) can live for much longer, but it is unclear whether CMMC generation is preserved in these mice also lacking the endothelin-3 gene. The aim of this study was to determine whether CMMC exist in ls/ls mouse colon and, if so, whether their existence and frequency are related to the length of aganglionosis. Spatiotemporal mapping and mechanical recordings of colonic wall movements were made from isolated whole colons obtained from wild-type and ls/ls mice. Although ls/ls mice had a megacolon, they still generated CMMC in the ganglionic segment, which on some occasions could propagate short distances into the aganglionic region. There was large variability in aganglionosis length, which showed a weak correlation with the existence or frequency of CMMC. Interestingly, CMMC propagation velocity was slower in ls/ls mice when evoked by intraluminal fluid. A myogenic motor pattern was identified in the aganglionic region that was maintained under tonic inhibition. We show that despite megacolon, ls/ls mice still generate CMMC in the ganglionic region. These offspring have sufficient propulsive motility in the ganglionic segment to live a normal murine lifespan and rarely die of bowel obstruction.
authors.affiliation: Discipline of Human Physiology, Center for Neuroscience, School of Medicine, Flinders University of South Australia, Adelaide, SA, Australia.
authors.forename: Kyra J
authors.initials: KJ
authors.lastname: Barnes
authors.forename: Nick J
authors.initials: NJ
authors.lastname: Spencer
mesh_terms: D000818:Animals; D003106:Colon / Q000187:drug effects / Q000502:physiology*; D019334:Endothelin-3 / Q000172:deficiency* / Q000235:genetics*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005260:Female; D017353:Gene Deletion; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D016065:Myoelectric Complex, Migrating / Q000187:drug effects / Q000235:genetics*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors
chemical_list: D019334:Endothelin-3; D004791:Enzyme Inhibitors; D019001:Nitric Oxide Synthase
keywords: colon; hirschsprung's disease; migrating motor complex; peristalsis