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Mouse models for congenital myopathies Mouse models for congenital myopathies

le 26 avril 2016
de 13h30 à 14h30

Séminaire de Laurent Pelletier (GIN)

The sarcoplasmic reticulum calcium channel ryanodine receptor RyR1, in association with the voltage gated calcium channel dihydropyridine receptor (DHPR) and numerous regulating proteins, form the skeletal muscle calcium release complex responsible for the excitation-contraction coupling process in skeletal muscle.

Mutations in the RYR1 gene have been associated with congenital myopathies such as Central Core Disease (CCD). CCD is characterized by the presence of cores in type 1 muscle fibers, which are large areas of abnormal myofibrillar architecture with sarcomeric disorganization and absence of mitochondria. Clinical presentations are heterogeneous ranging from mild phenotype, with moderate hypotonia during early childhood, delayed motor abilities, and slowly progressive proximal muscle weakness, to severe phenotype, including fetal akinesia, respiratory insufficiency at birth and generalized muscle weakness.

Two mouse models are under development in the team.

The first one is an inducible and muscle-specific RyR1 KO, which reproduces the situation observed in patients for whom mutations in the RyR1 gene result in protein deletion. This model is the first model for Central Core Disease, and its characterization will lead to a better understanding of the pathophysiology.

The second model is developed for a gene therapy project, based on exon skipping. It will be used to assess the in vivo efficacy and toxicity of the strategy developed in the team to correct a mutation in a very severely affected child.

Mise à jour le 22 octobre 2016

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