Accelerated intestinal transit in inbred mice with an increased number of interstitial cells of Cajal

Abstract

The interstitial cells of Cajal (ICC) play an important role in coordinating intestinal motility, and structural alterations in ICC are found in several human digestive diseases. Mouse models with defects in ICC allow a better understanding of their functions. We investigated the pattern of intestinal motility and the distribution of ICC in the PRM/Alf inbred mouse strain, characterized by a selective intestinal lengthening. In PRM/Alf mice, the digestive transit time, evaluated by using thermophilic Bacillus subtilis spores, was normal, indicating accelerated transit. The contractility and slow-wave frequency, recorded on isolated segments from the proximal small intestine, were significantly increased. The number of ICC was also significantly higher along the small intestine and the colon. The concomitant increase of the contractility, the slow-wave frequency, and the number of ICC is consistent with the proposal of a role of ICC number increase in the higher intestinal transit speed. The PRM/Alf model should be useful to further investigate the roles of ICC in the control of digestive motility. gut length; kit receptor; electrical slow waves; gastrointestinal motility; genetic model INTRINSIC AND EXTRINSIC NEUROHUMORAL signals control intestinal motility. An essential part of the system is the electrical pacemaker activity that originates in interstitial cells of Cajal (ICC). These cells are present in close association with smooth muscle cells and neurons of the gastrointestinal tract. In the mouse, ICC are fully differentiated at weaning, when the animals are given adult diet (13). The possible role of ICC in coordinating the contractile activity of the intestine has come to light in recent years (17,38). Alterations of ICC were reported in a variety of gastrointestinal disorders, including hypertrophic pyloric stenosis (24, 35, 41), Hirschsprung's disease (37,42,43), and intestinal pseudo-obstructions (19,21,44). Study of mouse models has proven to be a valuable strategy for studying the cause-and-effect relationship between ICC and motility problems, and Kit/W and SCF/Steel mutant mice have been instrumental in the study of the physiological roles of ICC (reviewed in Ref. 30). The Kit signaling pathway is essential for the development and maintenance of ICC (26). Both Kit and Steel mutant mice exhibit absence of electrical rhythmicity (i.e., slow waves) associated with underdevelopment of certain classes of ICC, including ICC of the small intestine that lie in the plane of the myenteric plexus (ICC-MP) between the circular and longitudinal muscle layers (17,38,39). The absence of ICC and slow waves in the small intestine of Kit mutant mice was paralleled with altered peristaltic movements of intestinal contents (10). However, it remains difficult to predict how abnormalities in ICC could influence digestive motor activity in vivo, because peristalsis is controlled by multiple, simultaneously operating mechanisms, in particular within the enteric nervous system (34). Indeed, migrating motor complexes can b...

Association of germ-free mice with a simplified human intestinal microbiota results in a shortened intestine

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The Role of Small-Intestinal P450 Enzymes in Protection against Systemic Exposure of Orally Administered Benzo[a]Pyrene

“…5B). The results from the 24-h time point also serve to exclude the possibility of contamination of the SI and colon tissue samples by extracellular BaP from the intestinal tract, given the reported transit time for foods through the gastrointestinal tract: ϳ15 h in rats (DeSesso and Jacobson, 2001) and ϳ10 to 11 h in mice (Bellier et al, 2005). Thus, not only can the loss of intestinal P450 activity lead to higher circulating BaP levels but also it can cause significant increases in the tissue burden of the toxicant in the gut and various extra-gut target organs, in mice exposed to BaP through oral ingestion.…”

Effect of electroacupuncture on gastric interstitial cells of Cajal in a rat model of diabetic gastroparesis

“…It was also found that the number of gastric ICCs in the EA group was greater than that in the model group. It has been suggested that the acceleration of intestinal transition may increase the numbers of ICCs (23). The pathological damage to the ICCs, as well as the nerve endings between ICCs and SMCs, was less than that in the model group, and the structures were more distinct and tightly connected.…”