Ultrastructural changes in diaphragm neuromuscular junctions in a severe mouse model for Spinal Muscular Atrophy and their prevention by bifunctional U7 snRNA correcting SMN2 splicing

Voigt, Tilman; Meyer, Kathrin; Baum, Oliver; Schümperli, Daniel (2010). Ultrastructural changes in diaphragm neuromuscular junctions in a severe mouse model for Spinal Muscular Atrophy and their prevention by bifunctional U7 snRNA correcting SMN2 splicing. Neuromuscular disorders, 20(11), pp. 744-52. Amsterdam: Elsevier 10.1016/j.nmd.2010.06.010

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In Spinal Muscular Atrophy (SMA), the SMN1 gene is deleted or inactivated. Because of a splicing problem, the second copy gene, SMN2, generates insufficient amounts of functional SMN protein, leading to the death of spinal cord motoneurons. For a "severe" mouse SMA model (Smn -/-, hSMN2 +/+; with affected pups dying at 5-7 days), which most closely mimicks the genetic set-up in human SMA patients, we characterise SMA-related ultrastructural changes in neuromuscular junctions (NMJs) of two striated muscles with discrete functions. In the diaphragm, but not the soleus muscle of 4-days old SMA mice, mitochondria on both sides of the NMJs degenerate, and perisynaptic Schwann cells as well as endoneurial fibroblasts show striking changes in morphology. Importantly, NMJs of SMA mice in which a modified U7 snRNA corrects SMN2 splicing and delays or prevents SMA symptoms are normal. This ultrastructural study reveals novel features of NMJ alterations - in particular the involvement of perisynaptic Schwann cells - that may be relevant for human SMA pathogenesis.

Item Type:	Journal Article (Original Article)
Division/Institute:	04 Faculty of Medicine > Pre-clinic Human Medicine > Institute of Anatomy > Topographical and Clinical Anatomy 04 Faculty of Medicine > Pre-clinic Human Medicine > Institute of Anatomy > Functional Anatomy 08 Faculty of Science > Department of Biology > Institute of Cell Biology
UniBE Contributor:	Voigt, Tilman, Baum, Oliver, Schümperli, Daniel
ISSN:	0960-8966
Publisher:	Elsevier
Language:	English
Submitter:	Factscience Import
Date Deposited:	04 Oct 2013 14:09
Last Modified:	05 Dec 2022 14:00
Publisher DOI:	10.1016/j.nmd.2010.06.010
PubMed ID:	20832308
Web of Science ID:	000284444200011
URI:	https://boris.unibe.ch/id/eprint/931 (FactScience: 201528)