山梨医科大学雑誌　第13巻2号　053-063(1998)

Experimental Pacemaker Disease Model in Mouse Intestine:
Impairment of Interstitial Cells of Cajar by an Antagonistic Antibody for c-kit

Ichiro Takayama, Morio Takeda, Shinichi Ohno, and Masayuki A. Fujino

Abstract: An antagonistic antibody, ACK2, for c-kit receptor tyrosine kinase was injected into newborn BALB/c mice to block c-kit expression. The experimental mice, which were inhibited against the expression of c-kit by the ACK2 injection, presented severe paralytic ileus. On the 12th day from birth, normal control mice presented c-kit immunoreaction spreading between longitudinal and circular smooth muscle layers of the duodenum, although such immunoreaction did not exist in the myenteric ganglions. That is, the distribution of ACK2-immunoreaction was identical to the localization of the interstitial cells of Cajal (ICC) in the region of the myenteric plexus. In addition, immunoreactions for neuropeptides such as Substance P or vasoactive intestinal peptide presented no remarkable differences between the control and the experimental mice. Electron microscopic examination confirmed ultrastructural impairment of ICC in experimental mice. In comparison with the ICC of control mice, the ICC in the experimental mice dramatically decreased in number and presented an altered ultrastructure with insufficient development of organelles such as mitochondria and Golgi apparatus. Such changes in ICC might be related to the dysmotility of the gut in experimental mice. The c-kit expression in newborn mice could be essential for the development of ICC networks or the non-neural intestinal pacemaker system.

Key words: Intestinal pacemaker, Interstitial cells of Cajal, c-kit, Special smooth muscle, Mouse.




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