期刊
NEUROMUSCULAR DISORDERS
卷 20, 期 11, 页码 744-752出版社
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.nmd.2010.06.010
关键词
Spinal Muscular Atrophy; Neuromuscular junctions; Diaphragm; Perisynaptic Schwann cells; Mouse models
资金
- Kanton Bern
- AFM (Association Francaise contre les Myopathies)
- EURASNET (European Network of Excellence on Alternative Splicing)
- Swiss Foundation for Research on Muscle Diseases
- Swiss National Science Foundation [3100A0-120064, 320030-120269]
- Swiss National Science Foundation (SNF) [320030-120269] Funding Source: Swiss National Science Foundation (SNF)
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. (C) 2010 Elsevier B.V. All rights reserved.
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