Selective loss of vagal intramuscular mechanoreceptors in mice mutant for steel factor, the c-Kit receptor ligand

Abstract

Vagal intramuscular arrays are mechanoreceptors that innervate smooth muscle fibers and intramuscular interstitial cells of Cajal of the proximal GI tract. C-Kit mutant mice that lack intramuscular interstitial cells of Cajal also lack intramuscular arrays. Mice mutant for steel factor, the ligand for the c-Kit receptor, were studied to extend and validate these previous findings and to characterize associated changes in food intake. Injections of wheat germ agglutinin-horseradish peroxidase and of dextran into the nodose ganglion were employed to label intramuscular arrays and intraganglionic laminar endings, the other vagal mechanoreceptors found in the gut wall. These two receptor types were inventoried in wholemounts of the stomach and duodenum using a standardized sampling and quantification regime. Steel mutants exhibited a paucity of normal intramuscular arrays and lacked intramuscular interstitial cells of Cajal in the forestomach, whereas their intraganglionic laminar endings appeared normal in number, distribution, and morphology. These observations suggest that intramuscular array losses in steel and c-Kit mutants are specific and result from the elimination of the intramuscular interstitial cells of Cajal, the effect common to both mutations, not from interactions peculiar to background strains or non-specific effects. Double-labeling analyses of intramuscular arrays and intramuscular interstitial cells of Cajal reinforced the hypothesis based on previous findings in the c-Kit mice that these interstitial cells have a trophic effect on intramuscular array development and/or maintenance. Finally, meal pattern analyses revealed decreased meal size and increased meal frequency in steel mutants, with normal daily intake. These alterations suggest short-term feeding controls are affected by the loss of intramuscular arrays and/or intramuscular interstitial cells of Cajal, though long-term controls are unimpaired.