SMN deficiency negatively impacts red pulp macrophages and spleen development in mouse models of spinal muscular atrophy

Marie Therese Khairallah, Jacob Astroski, Sarah K. Custer, Elliot Androphy, Craig L. Franklin, Christian L. Lorson

Research output: Contribution to journalArticle

5 Citations (Scopus)

Abstract

Spinal muscular atrophy (SMA) is a progressive neurodegenerative disease that is the leading genetic cause of infantile death. It is caused by a severe deficiency of the ubiquitously expressed Survival Motor Neuron (SMN) protein. SMA is characterized by a-lower motor neuron loss and muscle atrophy, however, there is a growing list of tissues impacted by a SMN deficiency beyond motor neurons. The non-neuronal defects are observed in the most severe Type I SMA patients and most of the widely used SMA mouse models, however, as effective therapeutics are developed, it is unclear whether additional symptoms will be uncovered in longer lived patients. Recently, the immune system and inflammation has been identified as a contributor to neurodegenerative diseases such as ALS. To determine whether the immune system is comprised in SMA, we analyzed the spleen and immunological components in SMA mice. In this report, we identify: a significant reduction in spleen size in multiple SMA mouse models and a pathological reduction in red pulp and extramedullary hematopoiesis. Additionally, red pulp macrophages, a discrete subset of yolk sac-derived macrophages, were found to be altered in SMA spleens even in presymptomatic post-natal day 2 animals. These cells, which are involved in iron metabolismand the phagocytosis of erythrocytes and blood-borne pathogens are significantly reduced prior to the development of the neurodegenerative hallmarks of SMA, implying a differential role of SMN in myeloid cell ontogeny. Collectively, these results demonstrate that SMN deficiency impacts spleen development and suggests a potential role for immunological development in SMA.

Original languageEnglish (US)
Article numberddx008
Pages (from-to)932-941
Number of pages10
JournalHuman Molecular Genetics
Volume26
Issue number5
DOIs
StatePublished - Mar 1 2017

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Spinal Muscular Atrophy
Motor Neurons
Spleen
Macrophages
Neurodegenerative Diseases
Immune System
Blood-Borne Pathogens
Spinal Muscular Atrophies of Childhood
Extramedullary Hematopoiesis
Yolk Sac
Muscular Atrophy
Myeloid Cells
Phagocytosis
Cause of Death
Iron
Erythrocytes
Inflammation

ASJC Scopus subject areas

  • Molecular Biology
  • Genetics
  • Genetics(clinical)

Cite this

SMN deficiency negatively impacts red pulp macrophages and spleen development in mouse models of spinal muscular atrophy. / Khairallah, Marie Therese; Astroski, Jacob; Custer, Sarah K.; Androphy, Elliot; Franklin, Craig L.; Lorson, Christian L.

In: Human Molecular Genetics, Vol. 26, No. 5, ddx008, 01.03.2017, p. 932-941.

Research output: Contribution to journalArticle

Khairallah, Marie Therese ; Astroski, Jacob ; Custer, Sarah K. ; Androphy, Elliot ; Franklin, Craig L. ; Lorson, Christian L. / SMN deficiency negatively impacts red pulp macrophages and spleen development in mouse models of spinal muscular atrophy. In: Human Molecular Genetics. 2017 ; Vol. 26, No. 5. pp. 932-941.
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