Survival of motor neurone protein is required for normal postnatal development of the spleen

Alison K Thomson, Eilidh Somers, Rachael A. Powis, Hannah K. Shorrock, Kelley Murphy, Kathryn J. Swoboda, Thomas H. Gillingwater, Simon H Parson

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Abstract

Spinal muscular atrophy (SMA), traditionally described as a predominantly childhood form of motor neurone disease, is the leading genetic cause of infant mortality. Although motor neurones are undoubtedly the primary affected cell type, the severe infantile form of SMA (Type I SMA) is now widely recognised to represent a multisystem disorder where a variety of organs and systems in the body are also affected. Here, we report that the spleen is disproportionately small in the ‘Taiwanese’ murine model of severe SMA (Smn−/−;SMN2tg/0), correlated to low levels of cell proliferation and increased cell death. Spleen lacks its distinctive red appearance and presents with a degenerated capsule and a disorganised fibrotic architecture. Histologically distinct white pulp failed to form and this was reflected in an almost complete absence of B lymphocytes necessary for normal immune function. In addition, megakaryoctyes persisted in the red pulp. However, the vascular density remained unchanged in SMA spleen. Assessment of the spleen in SMA patients with the infantile form of the disease indicated a range of pathologies. We conclude that development of the spleen fails to occur normally in SMA mouse models and human patients. Thus, further analysis of immune function is likely to be required to fully understand the full extent of systemic disease pathology in SMA.
Original languageEnglish
Pages (from-to) 337–346
Number of pages10
JournalJournal of Anatomy
Volume230
Issue number2
Early online date11 Oct 2016
DOIs
Publication statusPublished - 2 Feb 2017

Keywords

  • SMN
  • megakaryocytes
  • patients
  • immunity
  • organ pathology

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    Thomson, A. K., Somers, E., Powis, R. A., Shorrock, H. K., Murphy, K., Swoboda, K. J., Gillingwater, T. H., & Parson, S. H. (2017). Survival of motor neurone protein is required for normal postnatal development of the spleen. Journal of Anatomy, 230(2), 337–346 . https://doi.org/10.1111/joa.12546