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Med Sci (Paris). 2019 Nov;35 Hors série n° 2:39-42. doi: 10.1051/medsci/2019182. Epub 2019 Dec 20.

[Unraveling the pathophysiology of Bethlem Myopathy using a unique zebrafish model for the disease].

[Article in French; Abstract available in French from the publisher]

Author information

Institut NeuroMyoGène, Université Lyon 1, Université de Lyon, UMR CNRS 5310, Inserm U1217, Lyon, France.
Institut de Génomique et Fonctionnelle de Lyon, ENS de Lyon, UMR CNRS 5242, INRA USC1370, Université Lyon 1, Lyon, France.


in English, French

Bethlem myopathy (BM) is a neuromuscular disease characterized by joint contractures and muscle weakness. BM is caused by mutations in one of the genes encoding one of the three α-chains of collagen VI (COLVI), a component of the skeletal muscle extracellular matrix. Nowadays, an unresolved question is to understand how alteration of COLVI located outside the muscle cells leads to functional modifications in muscle fibers. The zebrafish model col6a1Δex14 is currently the unique animal model of the disease since it is the only model to reproduce a mutation that is the most frequently found in BM patients. In patient and col6a1Δex14 zebrafish muscles, the structure of the sarcoplasmic reticulum has been found to be altered, thus suggesting dysfunction in intracellular Ca2+ handling and/or in ion channels that are known to control Ca2+ homeostasis and to play pivotal roles in muscle function and pathogenesis. Therefore, our project aims at exploring the properties of ion channels and intracellular Ca2+ regulation using electrophysiological approaches and intracellular Ca2+ measurement at rest and during activity in isolated muscle fibers from col6a1Δex14 zebrafish. On one hand, this project should contribute to decipher how alteration in an extracellular matrix component transduces pathogenic signals within muscle fiber and should possibly lead to identify therapeutic targets for this currently incurable disease. On the other hand, because functional studies on zebrafish muscle cells are scarce, this project will provide a sound database on the electrophysiological properties of this cell model.


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