Neuromuscular junction changes in a mouse model of charcot-marie-tooth disease type 4C

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• dc.contributor.author Cipriani, Silvia
• dc.contributor.author Phan, Vietxuan
• dc.contributor.author Médard, Jean-Jacques
• dc.contributor.author Horvath, Rita
• dc.contributor.author Lochmüller, Hanns
• dc.contributor.author Chrast, Roman
• dc.contributor.author Roos, Andreas
• dc.contributor.author Spendiff, Sally
• dc.date.accessioned 2019-11-21T12:50:23Z
• dc.date.available 2019-11-21T12:50:23Z
• dc.date.issued 2018
• dc.description.abstract The neuromuscular junction (NMJ) appears to be a site of pathology in a number of peripheral nerve diseases. Charcot-Marie-Tooth (CMT) 4C is an autosomal recessive, early onset, demyelinating neuropathy. Numerous mutations in the SH3TC2 gene have been shown to underlie the condition often associated with scoliosis, foot deformities, and reduced nerve conduction velocities. Mice with exon 1 of the Sh3tc2 gene knocked out demonstrate many of the features seen in patients. To determine if NMJ pathology is contributory to the pathomechanisms of CMT4C we examined NMJs in the gastrocnemius muscle of SH3TC2-deficient mice. In addition, we performed proteomic assessment of the sciatic nerve to identify protein factors contributing to the NMJ alterations and the survival of demyelinated axons. Morphological and gene expression analysis of NMJs revealed a lack of continuity between the pre- and post-synaptic apparatus, increases in post-synaptic fragmentation and dispersal, and an increase in expression of the gamma subunit of the acetylcholine receptor. There were no changes in axonal width or the number of axonal inputs to the NMJ. Proteome investigations of the sciatic nerve revealed altered expression of extracellular matrix proteins important for NMJ integrity. Together these observations suggest that CMT4C pathology includes a compromised NMJ even in the absence of changes to the innervating axon.
• dc.format.mimetype application/pdf
• dc.identifier.citation Cipriani S, Phan V, Médard JJ, Horvath R, Lochmüller H, Chrast R, Roos A, Spendiff S. Neuromuscular junction changes in a mouse model of charcot-marie-tooth disease type 4C. Int J Mol Sci. 2018; 19(12). pii: E4072. DOI 10.3390/ijms19124072
• dc.identifier.doi http://dx.doi.org/10.3390/ijms19124072
• dc.identifier.issn 1422-0067
• dc.identifier.uri http://hdl.handle.net/10230/42916
• dc.language.iso eng
• dc.publisher MDPI
• dc.relation.ispartof Int J Mol Sci. 2018; 19(12). pii: E4072
• dc.rights © 2018 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
• dc.rights.accessRights info:eu-repo/semantics/openAccess
• dc.rights.uri http://creativecommons.org/licenses/by/4.0/
• dc.subject.keyword Charcot-Marie-Tooth disease 4C
• dc.subject.keyword SH3TC2
• dc.subject.keyword Demyelination
• dc.subject.keyword Mouse models
• dc.subject.keyword Neuromuscular junction
• dc.subject.keyword Peripheral neuropathy
• dc.title Neuromuscular junction changes in a mouse model of charcot-marie-tooth disease type 4C
• dc.type info:eu-repo/semantics/article
• dc.type.version info:eu-repo/semantics/publishedVersion