Interstitial cells of Cajal in the gastrointestinal musculature of Wjic c-kit mutant mice

Abstract

Interstitial cells of Cajal (ICC) generate electrical rhythmicity and transduce neural signals in the gastrointestinal musculature. ICC express the proto-oncogene c-kit, a receptor tyrosine kinase, and are identified morphologically by c-Kit immunoreactivity. The c-kit gene is allelic with the murine white-spotting locus W, and mutations of c-kit are known as W mutations. W mutations affect various developmental aspects of hematopoietic cells, germ cells, melanocytes, mast cells and ICC. We examined Wjic/Wjic mutant mice that have a mutation in the tyrosine kinase domain resulting in severe loss of protein function. Wjic/Wjic homozygotes exhibited white coats and black eyes. The gross morphology of the gastrointestinal tract showed no abnormality in mutant mice other than a forestomach papilloma. In the stomach, intramuscular ICC (ICC-IM) were missing, and myenteric ICC (ICC-MY) were reduced in number. In the small intestine, the number of ICC-MY was severely reduced; however there was a normal distribution of deep muscular plexus ICC (ICC-DMP). In the cecum, the numbers of ICC-IM and ICC-MY were severely depleted. ICC-IM were almost entirely absent in the colon, whereas ICC-MY loss was restricted to the distal colon. Patterns of ICC deficiency were generally similar between Wjic/Wjic mice and W/Wv mutants, which lack a specific type of ICC. The enteric nervous system of the mutant mice appeared normal. From these findings, we conclude that Wjic/Wjic mice represent a distinct, novel genotype resulting in a lack of a specific type of ICC in the gastrointestinal musculature.