Résumé :
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An increasing number of muscular dystrophies have been linked to mutations in genes of extracellular matrix components. Collagen XXII is a marker of the myotendinousjunction but its function has not been investigated. We took advantage of the zebrafish model to decipher its role in vivo. Confocal immunofluorescence with antibodiesagainst the zebrafish protein reveals that the onset of collagen XXII expression by muscle cells is dependent on FGF signaling and that the protein is exclusively depositedat the myotendinous junction in embryos. Moprholino knockdown of collagen XXII results in hatching impairment and lack of motility, muscle weakness in response toelectric stimulation, and reduction of Akt expression, a key factor of muscle growth induced by muscle activity. Repeated muscle contraction induces massive muscledetachment, a phenotype that can be rescued by micro-injection of human COLXXII protein. Transmission electron microscopy shows that rupture occurs at the interfacebetween basement membrane and the collagen fibrils of the myosepta, equivalent to mammalian tendons, without affecting sarcolemma integrity. These data indicatethat COLXXII plays a pivotal role in the formation and maintenance of functional myotendinous junctions identifying col22a1 as a potential candidate gene for one of theorphan muscular dystrophies in human.
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