title: Survival of motor neurone protein is required for normal postnatal development of the spleen.
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.
authors.affiliation: Institute of Medical Sciences, University of Aberdeen, Aberdeen, Scotland.|Euan MacDonald Centre for Motor Neurone Disease Research, Edinburgh, Scotland.
authors.forename: Alison K
authors.initials: AK
authors.lastname: Thomson
authors.affiliation: Euan MacDonald Centre for Motor Neurone Disease Research, Edinburgh, Scotland.|Centre for Integrative Physiology, University of Edinburgh, Edinburgh, Scotland.
authors.forename: Eilidh
authors.initials: E
authors.lastname: Somers
authors.affiliation: Euan MacDonald Centre for Motor Neurone Disease Research, Edinburgh, Scotland.|Centre for Integrative Physiology, University of Edinburgh, Edinburgh, Scotland.
authors.forename: Rachael A
authors.initials: RA
authors.lastname: Powis
authors.affiliation: Euan MacDonald Centre for Motor Neurone Disease Research, Edinburgh, Scotland.|Centre for Integrative Physiology, University of Edinburgh, Edinburgh, Scotland.
authors.forename: Hannah K
authors.initials: HK
authors.lastname: Shorrock
authors.affiliation: Department of Biology, Morgan State University, Baltimore, MD, USA.
authors.forename: Kelley
authors.initials: K
authors.lastname: Murphy
authors.affiliation: Department of Neurology, Center for Human Genetics Research, Massachusetts General Hospital, Boston, MA, USA.
authors.forename: Kathryn J
authors.initials: KJ
authors.lastname: Swoboda
authors.affiliation: Euan MacDonald Centre for Motor Neurone Disease Research, Edinburgh, Scotland.|Centre for Integrative Physiology, University of Edinburgh, Edinburgh, Scotland.
authors.forename: Thomas H
authors.initials: TH
authors.lastname: Gillingwater
authors.affiliation: Institute of Medical Sciences, University of Aberdeen, Aberdeen, Scotland.|Euan MacDonald Centre for Motor Neurone Disease Research, Edinburgh, Scotland.
authors.forename: Simon H
authors.initials: SH
authors.lastname: Parson
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D049109:Cell Proliferation / Q000502:physiology; D006801:Humans; D051379:Mice; D008822:Mice, Transgenic; D009134:Muscular Atrophy, Spinal / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D013154:Spleen / Q000166:cytology / Q000254:growth & development* / Q000378:metabolism*; D055540:Survival of Motor Neuron 2 Protein / Q000172:deficiency* / Q000235:genetics
chemical_list: C000597152:SMN2 protein, mouse; D055540:Survival of Motor Neuron 2 Protein
keywords: SMN; immunity; megakaryocytes; organ pathology; patients