Résumé :
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Schwartz-Jampel syndrome (SJS) is a recessive disorder characterized by neuromyotonia with complex repetitive discharges at electromyography (EMG). SJS results from hypomorphic mutations of perlecan, a ubiquitous proteoglycan secreted within basement membranes (BM). The muscle hyperactivity in SJS is proposed to result from synaptic acetylcholinesterase (AChE) deficiency as perlecan is crucial for the anchorage of AChE at the neuromuscular junction (NMJ). However, EMG patterns typical of AChE deficiency at the NMJ is not observed in patients with SJS. To determine whether the AChE hypothesis is correct, we studied the mutants of our SJS mouse model (see the abstract of Bangratz et al. for details on the model). Partial AChE deficiency at the NMJ was seen in all striated muscles tested. Lack of pretzel-like organization of postsynaptic acetylcholine receptors, poor branching of nerve terminals, and partially denervated NMJs were also observed. These alterations probably resulted from the major loss of synaptic perlecan as no disorganization of the extrasynaptic muscle BM nor muscle degeneration were seen, that suggested a role of perlecan in the maturation and/or maintenance of the NMJ. However, the AChE deficiency seen at the NMJ was primary to the synaptic deficiency of perlecan and was not due to denervation events as checked by transcriptional and co-staining analyses. EMG performed on the mutants demonstrated the occurrence of neuromyotonic discharges without decrement during repetitive stimulation in all muscles tested except the diaphragm. Despite the absence of neuromyotonic discharges, measures of contractile force and synaptic transmission parameters on isolated hemidiaphragm preparations showed features of AChE deficiency. These results demonstrate an electrophysiological effect of the partial AChE deficiency seen at the NMJ, and suggest that the AChE deficiency is necessary but is not sufficient to induce the neuromyotonia in SJS.
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