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Communication Dans Un Congrès Année : 2020

MBNL loss of function in motoneurons and motor unit dysfunction in myotonic dystrophy

Résumé

Myotonic dystrophy type 1 (DM1) is a neuromuscular disease characterised by myotonia, progressive muscle weakness and atrophy, cardiac defects as well as cognitive impairments. DM1 is caused by CTG repeats expansion in the 3’UTR of the DMPK gene. Subsequent mutated RNAs, containing expanded CUG repeats, aggregate as ribonuclear inclusions that sequester Muscleblind-like (MBNL) RNA-binding proteins, impairing their functions in various tissues. MBNL proteins have been shown to have a pivotal role in the pathology and RNA metabolism abnormalities observed in DM1 are mainly attributable to MBNL loss of function. MBNL family is composed of MBNL1, 2 and 3. MBNL1 is mostly expressed in the skeletal muscle but also found in the brain, while MBNL2 is predominantly expressed in the brain and MBNL3 during embryonic development. While most studies on DM1 muscle pathology have focused on the skeletal muscle itself, various results suggest an impaired communication between motor neurons (MN) and skeletal muscle via the neuromuscular junctions. We aim to determine the consequences of MBNL functional loss on the motor unit physiology and its latter contribution to DM1 muscle alterations. To assess the effect of MBNL1 and MBNL2 loss-of-function specifically in MN to skeletal muscle, we have generated a conditional MN-Mbnl1/2-KO mouse model in which Mbnl1 and Mbnl2 are specifically invalidated in the MN. MN, Neuromuscular junction and muscle function of these mice are under investigation through histological, electrophysiological and molecular characterization.
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Dates et versions

hal-03999245 , version 1 (21-02-2023)

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  • HAL Id : hal-03999245 , version 1

Citer

Charles Frison-Roche, Julien Messéant, Ludovic Arandel, Mégane Lemaitre, Jeanne Lainé, et al.. MBNL loss of function in motoneurons and motor unit dysfunction in myotonic dystrophy. RNA virtual.. but so real !, Sorbonne Université, Nov 2020, Vidéo, France. ⟨hal-03999245⟩
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