Abstract / Description of output
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 language | English |
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Pages (from-to) | 4249-4259 |
Number of pages | 11 |
Journal | Human Molecular Genetics |
Volume | 23 |
Issue number | 16 |
Early online date | 1 Apr 2014 |
DOIs | |
Publication status | Published - 15 Aug 2014 |
Keywords / Materials (for Non-textual outputs)
- MOTOR-NEURON PROTEIN
- SMN GENE
- MOUSE MODEL
- SATELLITE CELLS
- MICE
- SURVIVAL
- IDENTIFICATION
- TRICHOSTATIN
- INACTIVATION
- PURIFICATION
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Lyndsay Murray
- Deanery of Biomedical Sciences - Senior Lecturer in Anatomy
- Centre for Discovery Brain Sciences
- Edinburgh Neuroscience
- Euan MacDonald Centre for Motor Neuron Disease Research
Person: Academic: Research Active