MBNL loss of function in motoneurons leads to motor unit dysfunction in myotonic dystrophy - Archive ouverte HAL Access content directly
Poster Communications Year : 2022

MBNL loss of function in motoneurons leads to motor unit dysfunction in myotonic dystrophy

Abstract

"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 the expression of CTG repeat expansions in the 3’UTR of the DMPK gene; subsequent mutant transcripts, containing expanded CUG repeats, aggregate as ribonuclear inclusions that sequester muscleblind-like (MBNL) RNA-binding proteins, impairing their functions in various tissues. RNA metabolism abnormalities observed in affected DM1 tissues are mainly attributable to MBNL family loss-of-function: MBNL1 is mostly expressed in skeletal muscles but also found in the brain; 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, prior reports suggest an impaired communication between MN and skeletal muscle. To assess the role of MBNL in MN, we generated a conditional mouse model invalidated for Mbnl1 and Mbnl2 in MN (MN-dKO). MN-dKO mice develop progressive motor abnormalities but also neuromuscular junction (NMJ) alterations indicating that MBNL compound loss-of-function in MN significantly affects NMJ structure and function. As NMJ are unaltered in young MN-dKO mice, deficiency in NMJ maintenance rather than development may be responsible for NMJ abnormalities observed in older mice. Identification of molecular alterations in MN of this mouse model as well as MBNL RNA targets in MN is ongoing. Altogether our work will help for a better knowledge of DM1 physiopathology. "
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Dates and versions

hal-04005838 , version 1 (27-02-2023)

Identifiers

  • HAL Id : hal-04005838 , version 1

Cite

Charles Frison-Roche, Steve Cottin, Jeanne Lainé, Ludovic Arandel, Marius Halliez, et al.. MBNL loss of function in motoneurons leads to motor unit dysfunction in myotonic dystrophy. 7th International Myology Congress, Sep 2022, Nice, France. ⟨hal-04005838⟩
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