FUNCTIONAL ANALYSIS OF THE DIGESTIVE TRACT IN MDX MICE

Duchenne muscular dystrophy (DMD) is a genetic disease caused by the absence of dystrophin, a protein localised at the inner face of the plasma membrane of different cells, and its absence leads to the chronic muscle degeneration characteristic of DMD. Different hypothesises have put forward to understand the relation between dystrophin and muscle dysfunction, as alteration in intracellular calcium handling and/or deficit in the function of nitric oxide (NO), a regulator of many physiological processes. Smooth muscle dystrophy has also been observed in DMD patients, in fact clinical evidence suggests functional alterations of the digestive smooth muscle. Difficulty in obtain human biopsy material has been circumvented using mdx mice, animal models for studying dystrophic process. Mdx mice show altered intestinal motor behaviour, as human DMD. So, since a pathology of dystrophin-deficient smooth muscle exists, studies on the smooth muscle from gastrointestinal (GI) tract could contribute to understand the pathogenic mechanisms of the disease. In fact, if dystrophin deficiency leads to intracellular calcium overload the activity of smooth muscle, which critically dependent upon it, will be particularly perturbed. Moreover, NO is one of the main control systems in GI tract, making this preparation suitable to correlate abnormalities in NO system to dysregulation of Ca2+. Using functional, pharmacological and electrophysiological approaches we plane to investigate the relation between dystrophin, cytoplasmatic Ca2+ homeostasis and NO in mdx GI tract. The results could get new information helpful to resolve the pathophysiology of dystrophic process and consequently to find novel therapeutic approaches for DMD.