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 journalArticle

Abstract

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
Volume23
Issue number9
Early online date2 Dec 2013
DOIs
Publication statusPublished - May 2014

Fingerprint

Spinal Muscular Atrophy
Schwann Cells
Motor Neurons
Spinal Cord
Intercostal Nerves
Myelin Proteins
Spinal Nerves
Pyramidal Tracts
Protein Stability
Protein Biosynthesis
Peripheral Nerves
Axons
Proteins

Keywords

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

Cite this

Hunter, Gillian ; Sarvestany Aghamaleky, Arwin ; Roche, Sarah ; Syme, Rebecca ; Gillingwater, Thomas . / SMN-dependent intrinsic defects in Schwann cells in mouse models of spinal muscular atrophy. In: Human Molecular Genetics. 2014 ; Vol. 23, No. 9. pp. 2235-2250.
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abstract = "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.",
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Hunter, G, Sarvestany Aghamaleky, A, Roche, S, Syme, R & Gillingwater, T 2014, 'SMN-dependent intrinsic defects in Schwann cells in mouse models of spinal muscular atrophy', Human Molecular Genetics, vol. 23, no. 9, pp. 2235-2250. https://doi.org/10.1093/hmg/ddt612

SMN-dependent intrinsic defects in Schwann cells in mouse models of spinal muscular atrophy. / Hunter, Gillian; Sarvestany Aghamaleky, Arwin; Roche, Sarah; Syme, Rebecca; Gillingwater, Thomas .

In: Human Molecular Genetics, Vol. 23, No. 9, 05.2014, p. 2235-2250.

Research output: Contribution to journalArticle

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