Restoration of SMN in Schwann cells reverses myelination defects and improves neuromuscular function in spinal muscular atrophy

Hum Mol Genet. 2016 Jul 1;25(13):2853-2861. doi: 10.1093/hmg/ddw141. Epub 2016 May 11.


Spinal muscular atrophy (SMA) is a neuromuscular disease caused by low levels of SMN protein, primarily affecting lower motor neurons. Recent evidence from SMA and related conditions suggests that glial cells can influence disease severity. Here, we investigated the role of glial cells in the peripheral nervous system by creating SMA mice selectively overexpressing SMN in myelinating Schwann cells (Smn-/-;SMN2tg/0;SMN1SC). Restoration of SMN protein levels restricted solely to Schwann cells reversed myelination defects, significantly improved neuromuscular function and ameliorated neuromuscular junction pathology in SMA mice. However, restoration of SMN in Schwann cells had no impact on motor neuron soma loss from the spinal cord or ongoing systemic and peripheral pathology. This study provides evidence for a defined, intrinsic contribution of glial cells to SMA disease pathogenesis and suggests that therapies designed to include Schwann cells in their target tissues are likely to be required in order to rescue myelination defects and associated disease symptoms.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Disease Models, Animal
  • Mice
  • Mice, Transgenic
  • Motor Neurons / metabolism
  • Muscular Atrophy, Spinal / metabolism
  • Myelin Sheath / metabolism
  • Nerve Degeneration / pathology
  • Neuroglia / metabolism*
  • Neuromuscular Diseases / pathology
  • Neuromuscular Junction / metabolism
  • Schwann Cells / metabolism
  • Spinal Cord / metabolism
  • Survival of Motor Neuron 1 Protein / genetics*
  • Survival of Motor Neuron 1 Protein / metabolism*
  • Survival of Motor Neuron 2 Protein / genetics
  • Survival of Motor Neuron 2 Protein / metabolism


  • SMN2 protein, mouse
  • Smn1 protein, mouse
  • Survival of Motor Neuron 1 Protein
  • Survival of Motor Neuron 2 Protein