Contenu

x

Moteur de recherche interne

Grenoble Institut des Neurosciences Grenoble Institut des Neurosciences

  • Youtube
  • Linkedin
  • Twitter

Accueil > Nous rejoindre > Offres de stages

Accéder au plan complet du site

What can we learn about RyR1-related myopathies using a mouse model?

Objectifs

Investigating events linking a gene mutation to the myopathy-associated muscle weakness. This research is performed at animal, tissue, cell and molecular levels, with both descriptive and functional criteria.

Résumé

Congenital myopathies, one of the top worldwide neuromuscular disorders, are characterized by impairment of skeletal muscles contraction causing muscle weakness. An inducible and muscle-specific mouse model of congenital myopathy has recently been established in our laboratory to better understand the physio-pathology and especially the importance of the Ryanodine receptor-1 (RyR1) in these myopathies. RyR1 is a calcium channel belonging to a complex responsible for the release of calcium from the sarcoplasmic reticulum to the cytosol, and responsible for muscle contraction.
First results show that our mouse model presents close similarities with human disease, especially the loss of muscle strength and weight. The purpose of this work is to characterize the defects associated with myopathy, either in vivo or at cellular level to better understand the cascade of events linking the alteration of a gene to the onset of disease. This will enable to offer new diagnostic and therapeutic perspectives.

Méthodes

In vivo experimentation, primary muscle cell culture, immuno-fluorescence, western blot, RT-qPCR, functional assay (cytosolic calcium imaging).

Références

  • Functional Characterization of a Central Core Disease RyR1 Mutation (p.Y4864H) Associated with Quantitative Defect in RyR1 Protein. Cacheux M, Blum A, Sébastien M, Wozny AS, Brocard J, Mamchaoui K, Mouly V, Roux-Buisson N, Rendu J, Monnier N, Krivosic R, Allen P, Lacour A, Lunardi J, Fauré J, Marty I. J Neuromuscul Dis. 2015 Nov 20;2(4):421-432
  • Null mutations causing depletion of the type 1 ryanodine receptor (RYR1) are commonly associated with recessive structural congenital myopathies with cores. Monnier N, Marty I, Faure J, Castiglioni C, Desnuelle C, Sacconi S, Estournet B, Ferreiro A, Romero N, Laquerriere A, Lazaro L, Martin JJ, Morava E, Rossi A, Van der Kooi A, de Visser M, Verschuuren C, Lunardi J. Hum Mutat. 2008 May;29(5):670-8. doi: 10.1002/humu.20696.
  • Triadin deletion induces impaired skeletal muscle function. Oddoux S., Brocard J., Schweitzer A., Szentesi P., Giannesini B., Brocard J., Fauré J., Pernet-Gallay K., Bendahan D., Lunardi J., Csernoch L., Marty I., J Biol Chem. (2009), 284, 34918-34929

Contacts

I. Marty, DR2 Inserm
Email : isabelle.marty@univ-grenoble-alpes.fr

Mise à jour le 23 mai 2017

Contacts

Pour une candidature spontanée, envoyez un email ou utilisez le formulaire de contact.

Pour les stages de licence et de 3ème, utilisez les formulaires de demande spécifiques : stage de 3ème ou stage de licence UGA. 

Membres
Associés renforcés
Associés simples