Ultrastructural changes in the interstitial cells of Cajal and gastric dysrhythmias in mice lacking full-length dystrophin (mdx mice)
Article first published online: 18 NOV 2003
Copyright © 2003 Wiley-Liss, Inc.
Journal of Cellular Physiology
Volume 199, Issue 2, pages 293–309, May 2004
How to Cite
Vannucchi, M.-G., Zizzo, M.-G., Zardo, C., Pieri, L., Serio, R., Mulè, F. and Faussone-Pellegrini, M.-S. (2004), Ultrastructural changes in the interstitial cells of Cajal and gastric dysrhythmias in mice lacking full-length dystrophin (mdx mice). J. Cell. Physiol., 199: 293–309. doi: 10.1002/jcp.10470
- Issue published online: 5 MAR 2004
- Article first published online: 18 NOV 2003
- Manuscript Accepted: 18 SEP 2003
- Manuscript Received: 3 JUN 2003
- Telethon-Italy. Grant Number: 1134
At least two populations of c-kit positive interstitial cells of Cajal (ICC) lie in the gastric wall, one located at the myenteric plexus level has a pace-making function and the other located intramuscularly is intermediary in the neurotransmission and regenerates the slow waves. Both of these ICC sub-types express full-length dystrophin. Mdx mice, an animal model lacking in full-length dystrophin and used to study Duchenne muscular dystrophy (DMD), show gastric dismotilities. The aim of the present study was to verify in mdx mice whether: (i) gastric ICC undergo morphological changes, through immunohistochemical and ultrastructural analyses; and (ii) there are alterations in the electrical activity, using intracellular recording technique. In control mice, ICC sub-types showed heterogeneous ultrastructural features, either intramuscularly or at the myenteric plexus level. In mdx mice, all of the ICC sub-types underwent important changes: coated vesicles were significantly more numerous and caveolae significantly fewer than in control; moreover, cytoskeleton and smooth endoplasmic reticulum were reduced and mitochondria enlarged. c-Kit-positivity and integrity of the ICC networks were maintained. In the circular muscle of normal mice slow waves, which consisted of initial and secondary components, occurred with a regular frequency. In mdx mice, slow waves occurred in a highly dysrhythmic fashion and they lacked a secondary component. We conclude that the lack of the full-length dystrophin is associated with ultrastructural modifications of gastric ICC, most of which can be interpreted as signs of new membrane formation and altered Ca2+ handling, and with defective generation and regeneration of slow wave activity. J. Cell. Physiol. 199: 293–309, 2004© 2003 Wiley-Liss, Inc.