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

Lookup NU author(s): Silvia Cipriani, Professor Rita HorvathORCiD, Professor Hanns Lochmuller, Dr Andreas Roos, Dr Sally Spendiff



This work is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0).


© 2018 by the authors. Licensee MDPI, Basel, Switzerland. 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.

Publication metadata

Author(s): Cipriani S, Phan V, Medard J-J, Horvath R, Lochmuller H, Chrast R, Roos A, Spendiff S

Publication type: Article

Publication status: Published

Journal: International Journal of Molecular Sciences

Year: 2018

Volume: 19

Issue: 12

Online publication date: 17/12/2018

Acceptance date: 14/12/2018

Date deposited: 09/01/2019

ISSN (print): 1661-6596

ISSN (electronic): 1422-0067

Publisher: MDPI AG


DOI: 10.3390/ijms19124072

PubMed id: 30562927


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Funder referenceFunder name
201064/Z/16/ZWellcome Trust
109915/Z/15/ZWellcome Trust
MR/N025431/1Medical Research Council (MRC)