Immunohistochemical characterization of interstitial cells of Cajal (ICC) in the mouse intestine using whole mount preparations – with particular reference to their density, morphological features, and network patterns

The aim of this study was to evaluate the distribution pattern of the different subtypes of the interstitial cells of Cajal (ICC), to understand their roles in gastrointestinal motility and interaction with the enteric nervous system depending on their location. Based on morphological analyses using the immunohistochemistry of whole mount preparations of mouse intestine, we investigated the normal local density and morphological features of ICC and statistically compared the number of the cells between the mesenteric and anti-mesenteric sides, and between the proximal and distal sites. Density gradients were shown in ICC associated with the deep muscular plexus, the myenteric plexus in the large intestine, and the longitudinal muscle. However, such changes in cell density were not always proportional to other subtypes, even in the same part of the intestine. As the pacemaker cells for intestinal motility, dense and seamless network connections were shown in ICC associated with the myenteric plexus in the small intestine and ICC associated with the submuscular plexus in the large intestine without any gradient of cell density, in contrast with the difference of morphological network patterns between proximal and distal sites. Thus, we conclude that the distribution patterns of ICC differ in cell density, morphological features, and network patterns, depending on the individual subtype and site of the intestine. Therefore, careful studies on the quantification and distribution of ICC under normal conditions should be important in diagnosing clinical disorders related to abnormal distribution of ICC.