Ultrastructural changes in the interstitial cells of Cajal and gastric dysrhythmias in mice lacking full-length dystrophin (mdx mice).
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 Ca(2+) handling, and with defective generation and regeneration of slow wave activity.
Vannucchi
Maria-Giuliana
MG
Department of Human Anatomy, Histology and Forensic Medicine, Section of Histology E. Allara, University of Florence, Florence, Italy.
Zizzo
Maria-Grazia
MG
Zardo
Claudio
C
Pieri
Laura
L
Serio
Rosa
R
Mulè
Flavia
F
Faussone-Pellegrini
Maria-Simonetta
MS
D000818:Animals; D004195:Disease Models, Animal; D016189:Dystrophin / Q000172:deficiency*; D004594:Electrophysiology; D007150:Immunohistochemistry; D008297:Male; D051379:Mice; D018101:Mice, Inbred mdx; D008854:Microscopy, Electron; D009130:Muscle, Smooth / Q000473:pathology / Q000502:physiology* / Q000648:ultrastructure; D009136:Muscular Dystrophies / Q000503:physiopathology*; D009197:Myenteric Plexus / Q000502:physiology / Q000648:ultrastructure; D019009:Proto-Oncogene Proteins c-kit / Q000378:metabolism; D013270:Stomach / Q000166:cytology* / Q000473:pathology* / Q000502:physiology
D016189:Dystrophin; D019009:Proto-Oncogene Proteins c-kit