Blood Flow to the Spleen is Altered in a Mouse Model of Spinal Muscular Atrophy

Article type: Short Communication

Authors: Deguise, Marc-Olivier^{a; b; c} | Beauvais, Ariane^a | Schneider, Bernard L.^{d; e} | Kothary, Rashmi^{a; b; c; f; *}

Affiliations: [a] Regenerative Medicine Program, Ottawa Hospital Research Institute, Ottawa, Ontario, Canada | [b] Department of Cellular and Molecular Medicine, University of Ottawa, Ottawa, Ontario, Canada | [c] Centre for Neuromuscular Disease, University of Ottawa, Ottawa, Ontario, Canada | [d] Bertarelli Foundation Gene Therapy Platform, School of Life Sciences, Ecole Polytechnique Fédérale de Lausanne (EPFL), 1202 Geneva, Switzerland | [e] Brain Mind Institute, 27218 Ecole Polytechnique Fédérale de Lausanne (EPFL), Lausanne, Switzerland | [f] Department of Biochemistry, Microbiology, and Immunology, Faculty of Medicine, and Department of Medicine, University of Ottawa, Ottawa, Ontario, Canada

Correspondence: [*] Correspondence to: Rashmi Kothary, Ottawa Hospital Research Institute, 501 Smyth Road, Ottawa, Ontario, Canada K1H 8L6. Tel: +1 613 737 8707, Fax: +1 613 737 8803; E-mail: [email protected].

Abstract: Spinal muscular atrophy (SMA) is a neuromuscular disorder affecting young children. While pre-clinical models of SMA show small spleens, the same is not true in humans. Here, we show by doppler ultrasonography decreased splenic blood flow in Smn2B/– mice. Further, AAV9-SMN gene therapy does not rescue the distal ear and tail necrosis nor the spleen size in these mice, suggesting that the latter may be linked to a cardiovascular defect. Absence of smaller spleens in human patients is likely due to differences in presentation of defects in SMA between pre-clinical mouse models and human patients, particularly the susceptibility to cardiovascular issues.

Keywords: Immune system, perfusion, blood flow, vasculature, mouse models

DOI: 10.3233/JND-200493

Journal: Journal of Neuromuscular Diseases, vol. 7, no. 3, pp. 315-322, 2020