| Title: |
In vivo RyR1 reduction in muscle triggers a core-like myopathy |
| Authors: |
Pelletier, Laurent; Petiot, Anne; Brocard, Julie; Giannesini, Benoit; Giovannini, Diane; Sanchez, Colline; Travard, Lauriane; Chivet, Mathilde; Beaufils, Mathilde; Kutchukian, Candice; Bendahan, David; Metzger, Daniel; Armstrong, Clara; Romero, Norma; Rendu, John; Jacquemond, Vincent; Fauré, Julien; Marty, Isabelle |
| Contributors: |
Groupe d'imagerie neurofonctionnelle (GIN); Institut des Maladies Neurodégénératives Bordeaux (IMN); Université de Bordeaux (UB)-Centre National de la Recherche Scientifique (CNRS)-Université de Bordeaux (UB)-Centre National de la Recherche Scientifique (CNRS)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA); Centre de résonance magnétique biologique et médicale (CRMBM); Aix Marseille Université (AMU)-Assistance Publique - Hôpitaux de Marseille (APHM)-Centre National de la Recherche Scientifique (CNRS); Institut NeuroMyoGène (INMG); Université Claude Bernard Lyon 1 (UCBL); Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM) |
| Source: |
ISSN: 0001-6322. |
| Publisher Information: |
HAL CCSD; Springer Verlag |
| Publication Year: |
2020 |
| Collection: |
Archive ouverte HAL (Hyper Article en Ligne, CCSD - Centre pour la Communication Scientifique Directe) |
| Subject Terms: |
RyR1 reduction induces a myopathy Ryanodine receptor; Calcium; skeletal muscle; excitation-contraction coupling; congenital myopathies; mouse model; [SDV]Life Sciences [q-bio] |
| Description: |
International audience ; 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. |
| Document Type: |
article in journal/newspaper |
| Language: |
English |
| Relation: |
hal-03021986; https://hal-cnrs.archives-ouvertes.fr/hal-03021986; https://hal-cnrs.archives-ouvertes.fr/hal-03021986/document; https://hal-cnrs.archives-ouvertes.fr/hal-03021986/file/2020.08.27.269647v1.full.pdf |
| DOI: |
10.1101/2020.08.27.269647 |
| Availability: |
https://hal-cnrs.archives-ouvertes.fr/hal-03021986; https://hal-cnrs.archives-ouvertes.fr/hal-03021986/document; https://hal-cnrs.archives-ouvertes.fr/hal-03021986/file/2020.08.27.269647v1.full.pdf; https://doi.org/10.1101/2020.08.27.269647 |
| Rights: |
info:eu-repo/semantics/OpenAccess |
| Accession Number: |
edsbas.844BCBB4 |
| Database: |
BASE |