IMPAIRED DEVELOPMENT OF INTERSTITIAL-CELLS AND INTESTINAL ELECTRICAL RHYTHMICITY IN STEEL MUTANTS

Electrical rhythmicity in the gastrointestinal tract may originate in interstitial cells of Cajal (IC). Development of IC in the small intes tine is linked to signaling via the tyrosine kinase receptor, c-Kit. I C express c-kit protein, and disruption of c-Kit signaling causes brea kdown in IC networks and loss of slow waves. We tested whether mutatio ns in steel factor, the ligand for c-Kit, affect the development of IC networks. IC were found in the region of the myenteric plexus (IC-MY) in mice with steel mutations (i.e., Sl/Sl(d)) at 5-10 days postpartum , but these cells formed an abnormal network. IC-MY were not observed in adult Sl/Sl(d) animals. IC in the deep muscular plexus (IC-DMP) app eared normal in Sl/Sl(d) animals. Electrical slow waves, normally pres ent in the small intestine, were absent in Sl/Sl(d) animals (10-30 day s postpartum). Neural inputs were intact in Sl/Sl(d) animals. Steel fa ctor appears important for the development of certain classes of IC, a nd IC-MY appear to be involved in the generation of electrical rhythmi city in the small intestine.