SMN-dependent intrinsic defects in Schwann cells in mouse models of spinal muscular atrophy

Gillian Hunter, Arwin Sarvestany Aghamaleky, Sarah Roche, Rebecca Syme, Thomas Gillingwater

Research output: Contribution to journalArticlepeer-review


Low levels of survival of motor neuron (SMN) protein lead to spinal muscular atrophy (SMA). The major pathological hallmark of SMA is a loss of lower motor neurons from spinal cord and peripheral nerve. However, recent studies have revealed pathological changes in other cells and tissues of the neuromuscular system. Here, we demonstrate intrinsic, SMN-dependent defects in Schwann cells in SMA. Myelination in intercostal nerves was perturbed at early- and late-symptomatic stages of disease in two mouse models of SMA. Similarly, maturation of axo–glial interactions at paranodes was disrupted in SMA mice. In contrast, myelination of motor axons in the corticospinal tract of the spinal cord occurred normally. Schwann cells isolated from SMA mice had significantly reduced levels of SMN and failed to express key myelin proteins following differentiation, likely due to perturbations in protein translation and/or stability rather than transcriptional defects.
Original languageEnglish
Pages (from-to)2235-2250
Number of pages16
JournalHuman Molecular Genetics
Issue number9
Early online date2 Dec 2013
Publication statusPublished - May 2014


  • spinal muscular atrophy
  • motor neurons
  • neuromuscular system
  • spinal cord


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