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In vivo RyR1 reduction in muscle triggers a core-like myopathy

Abstract : Some mutations in the RYR1 gene lead to congenital myopathies, through reduction in this calcium channel expression level, but the functional whole organism consequences of reduction in RyR1 amount have never been studied. We have developed and characterized a mouse model with inducible muscle specific RYR1 deletion. Recombination in the RYR1 gene resulted in a progressive reduction in the protein amount and was associated with a progressive muscle weakness and atrophy. Calcium fluxes in isolated muscle fibers were accordingly reduced. Alterations in the muscle structure were observed, with fibers atrophy, abnormal mitochondria distribution, membrane remodeling, associated with increase in the expression level of many proteins and inhibition of the autophagy process. This model demonstrates that RyR1 reduction is sufficient to recapitulate most features of Central Core Disease, and accordingly similar alterations were observed in muscle biopsies from Central Core Disease patients, pointing to common pathophysiological mechanisms related to RyR1 reduction.
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https://hal-cnrs.archives-ouvertes.fr/hal-03021986
Contributor : Daniel Metzger <>
Submitted on : Tuesday, November 24, 2020 - 3:47:16 PM
Last modification on : Monday, November 30, 2020 - 6:03:14 PM
Long-term archiving on: : Thursday, February 25, 2021 - 8:28:56 PM

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Laurent Pelletier, Anne Petiot, Julie Brocard, Benoit Giannesini, Diane Giovannini, et al.. In vivo RyR1 reduction in muscle triggers a core-like myopathy. Acta Neuropathologica, Springer Verlag, 2020, ⟨10.1101/2020.08.27.269647⟩. ⟨hal-03021986⟩

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