No 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 Ca(2+) handling, and with defective generation and regeneration of slow wave activity.

A gene located on the X chromosome is responsible for the transcription of several mRNA and related dystrophin isoforms. Lack or truncated expression of the 427-kDa, full-length isoform in skeletal muscle results in Duchenne muscular dystrophy (DMD). Patients with DMD, as well as mdx mice, a mutant strain also lacking this isoform, show gastrointestinal dismotilities. The present aim was to identify the cell types that express full-length dystrophin in the gastrointestinal tract. An immunohistochemical study was performed using an antibody specific for this isoform, and double labelings were made for interstitial cells of Cajal (ICC) identification and to verify whether all neurons express full-length dystrophin. Three different fixation procedures were used. The results showed that ICC, enteric neurons, and smooth muscle and myoid cells expressed full-length dystrophin. In ICC and neurons, dystrophin-immunoreactive patches were irregularly distributed at the cell contour and within the cytoplasm. In smooth muscle and myoid cells, regularly spaced dystrophin-immunoreactive bars were located along the cell contour. Labeling intensity varied according to fixation procedure. The different subcellular distributions of dystrophin immunoreactivity might reflect diverse roles played by full-length isoforms in each cell type. Dystrophin loss in cells involved in gastrointestinal motility might explain the gastrointestinal symptomatology affecting DMD patients and mdx mice.

No abstract

No abstract