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Ultrastructural changes in the interstitial cells of Cajal and gastric dysrhythmias in mice lacking full-length dystrophin (mdx mice)

Authors

  • Maria-Giuliana Vannucchi,

    1. Department of Human Anatomy, Histology and Forensic Medicine, Section of Histology “E. Allara,” University of Florence, Florence, Italy
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  • Maria-Grazia Zizzo,

    1. Department of Cellular and Developmental Biology, University of Palermo, Viale delle Scienze, Palermo, Italy
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  • Claudio Zardo,

    1. Department of Human Anatomy, Histology and Forensic Medicine, Section of Histology “E. Allara,” University of Florence, Florence, Italy
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  • Laura Pieri,

    1. Department of Human Anatomy, Histology and Forensic Medicine, Section of Histology “E. Allara,” University of Florence, Florence, Italy
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  • Rosa Serio,

    1. Department of Cellular and Developmental Biology, University of Palermo, Viale delle Scienze, Palermo, Italy
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  • Flavia Mulè,

    1. Department of Cellular and Developmental Biology, University of Palermo, Viale delle Scienze, Palermo, Italy
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  • Maria-Simonetta Faussone-Pellegrini

    Corresponding author
    1. Department of Human Anatomy, Histology and Forensic Medicine, Section of Histology “E. Allara,” University of Florence, Florence, Italy
    • Department of Human Anatomy, Histology and Forensic Medicine, University of Florence, Viale Pieraccini 6, 50139 Florence, Italy.
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Abstract

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.

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