Interstitial cells of Cajal in the gastrointestinal musculature of W mutant mice

Interstitial cells of Cajal (ICC) are important regulatory cells generating electrical rhythmicity and transducing neural signals in the gastrointestinal musculature. ICC express the proto-oncogene c-kit, a receptor tyrosine kinase, and can be examined morphologically using the c-kit antibody. The c-kit gene is allelic with the murine white-spotting locus W, and the c-kit mutation (W mutation) affects various aspects of hematopoietic cells, germ cells, melanocytes, mast cells, and ICC. Heterozygous W/W-v mutant mice lack a specific type of ICC and have been used to reveal its function. To search for a new model that lacks a specific type of ICC, we examined homozygous W-v/W-v black-eyed-white mice that are viable with anemia. Results showed the principal patterns of ICC deficiency were the same between the W/W-v and W-v/W-v mutants. In the stomach of both mice, 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 in spite of a normal distribution of deep muscular plexus ICC (ICC-DMP). The cecum also exhibited fewer reduced. ICC-IM in the colon were almost entirely missing, whereas ICC-MY were reduced only in the distal colon. In the small intestine and colon, the number of remaining ICC-MY in W-v/W-v mice was greater than that in W/W-v mice. The enteric nervous system of the two mutant mice showed normal characteristics. From these findings, we conclude that W-v/W-v mice represent a new genotype that lacks a part of the ICC in its gastrointestinal musculature.