Myogenic program dysregulation is contributory to disease pathogenesis in spinal muscular atrophy

Justin G. Boyer, Marc-Olivier Deguise, Lyndsay M. Murray, Armin Yazdani, Yves De Repentigny, Céline Boudreau-Larivière, Rashmi Kothary*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

Abstract

Mutations in the survival motor neuron (SMN1) gene lead to the neuromuscular disease spinal muscular atrophy (SMA). Although SMA is primarily considered as a motor neuron disease, the importance of muscle defects in its pathogenesis has not been fully examined. We use both primary cell culture and two different SMA model mice to demonstrate that reduced levels of Smn lead to a profound disruption in the expression of myogenic genes. This disruption was associated with a decrease in myofiber size and an increase in immature myofibers, suggesting that Smn is crucial for myogenic gene regulation and early muscle development. Histone deacetylase inhibitor trichostatin A treatment of SMA model mice increased myofiber size, myofiber maturity and attenuated the disruption of the myogenic program in these mice. Taken together, our work highlights the important contribution of myogenic program dysregulation to the muscle weakness observed in SMA.

Original languageEnglish
Pages (from-to)4249-4259
Number of pages11
JournalHuman Molecular Genetics
Volume23
Issue number16
Early online date1 Apr 2014
DOIs
Publication statusPublished - 15 Aug 2014

Keywords

  • MOTOR-NEURON PROTEIN
  • SMN GENE
  • MOUSE MODEL
  • SATELLITE CELLS
  • MICE
  • SURVIVAL
  • IDENTIFICATION
  • TRICHOSTATIN
  • INACTIVATION
  • PURIFICATION

Fingerprint

Dive into the research topics of 'Myogenic program dysregulation is contributory to disease pathogenesis in spinal muscular atrophy'. Together they form a unique fingerprint.

Cite this