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.
journal_name
Hum Mol Genetjournal_title
Human molecular geneticsauthors
Boyer JG,Deguise MO,Murray LM,Yazdani A,De Repentigny Y,Boudreau-Larivière C,Kothary Rdoi
10.1093/hmg/ddu142subject
Has Abstractpub_date
2014-08-15 00:00:00pages
4249-59issue
16eissn
0964-6906issn
1460-2083pii
ddu142journal_volume
23pub_type
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