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

JG Boyer, MO Deguise, LM Murray… - Human molecular …, 2014 - academic.oup.com
JG Boyer, MO Deguise, LM Murray, A Yazdani, Y De Repentigny, C Boudreau-Larivière
Human molecular genetics, 2014academic.oup.com
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 …
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.
Oxford University Press