{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T07:15:51Z","timestamp":1791270951408,"version":"4.1.0"},"reference-count":56,"publisher":"MDPI AG","issue":"12","license":[{"start":{"date-parts":[[2018,12,17]],"date-time":"2018-12-17T00:00:00Z","timestamp":1545004800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100007393","name":"Association Fran\u00e7aise contre les Myopathies","doi-asserted-by":"publisher","award":["21644"],"award-info":[{"award-number":["21644"]}],"id":[{"id":"10.13039\/100007393","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100010269","name":"Wellcome Trust","doi-asserted-by":"publisher","award":["201064\/Z\/16\/Z"],"award-info":[{"award-number":["201064\/Z\/16\/Z"]}],"id":[{"id":"10.13039\/100010269","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>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.<\/jats:p>","DOI":"10.3390\/ijms19124072","type":"journal-article","created":{"date-parts":[[2018,12,18]],"date-time":"2018-12-18T02:15:59Z","timestamp":1545099359000},"page":"4072","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":30,"title":["Neuromuscular Junction Changes in a Mouse Model of Charcot-Marie-Tooth Disease Type 4C"],"prefix":"10.3390","volume":"19","author":[{"given":"Silvia","family":"Cipriani","sequence":"first","affiliation":[{"name":"John Walton Muscular Dystrophy Research Centre, Newcastle University, Newcastle upon Tyne NE1 3BZ, UK"},{"name":"INSPE-Institute of Experimental Neurology, San Raffaele Scientific Institute, 20132 Milan, Italy"},{"name":"Division of Neuroscience, San Raffaele Scientific Institute, 20132 Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vietxuan","family":"Phan","sequence":"additional","affiliation":[{"name":"Leibniz-Institut f\u00fcr Analytische Wissenschaften -ISAS- e.V.; Otto-Hahn-Strasse 6b, 44227 Dortmund, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jean-Jacques","family":"M\u00e9dard","sequence":"additional","affiliation":[{"name":"Department of Neuroscience, Karolinska Institutet, 171 65 Stockholm, Sweden"},{"name":"Department of Clinical Neuroscience, Karolinska Institutet, 171 65 Stockholm, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rita","family":"Horvath","sequence":"additional","affiliation":[{"name":"Department of Clinical Neurosciences, University of Cambridge, John Van Geest Cambridge Centre for Brain Repair, Forvie, Robinson way, Cambridge Biomedical Campus, Cambridge CB2 0PY, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2324-8001","authenticated-orcid":false,"given":"Hanns","family":"Lochm\u00fcller","sequence":"additional","affiliation":[{"name":"Department of Neuropediatrics and Muscle Disorders, Medical Center-University of Freiburg, Mathildenstrasse 1, 79106 Freiburg, Germany"},{"name":"Centro Nacional de An\u00e1lisis Gen\u00f3mico, Center for Genomic Regulation, Barcelona Institute of Science and Technology, Baldri I reixac 4, 08028 Barcelona, Spain"},{"name":"Children\u2019s Hospital of Eastern Ontario Research Institute, University of Ottawa, Ottawa, ON K1H 8L1, Canada"},{"name":"Division of Neurology, Department of Medicine, The Ottawa Hospital, Riverside Drive, Ottawa, ON K1H 7X5, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roman","family":"Chrast","sequence":"additional","affiliation":[{"name":"Department of Neuroscience, Karolinska Institutet, 171 65 Stockholm, Sweden"},{"name":"Department of Clinical Neuroscience, Karolinska Institutet, 171 65 Stockholm, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2833-0928","authenticated-orcid":false,"given":"Andreas","family":"Roos","sequence":"additional","affiliation":[{"name":"Leibniz-Institut f\u00fcr Analytische Wissenschaften -ISAS- e.V.; Otto-Hahn-Strasse 6b, 44227 Dortmund, Germany"},{"name":"Department of Neuropediatrics, Developmental Neurology and Social Pediatrics, Centre for Neuromuscular Disorders in Children, University Children\u2019s Hospital Essen, University of Duisburg-Essen, 45122 Essen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sally","family":"Spendiff","sequence":"additional","affiliation":[{"name":"John Walton Muscular Dystrophy Research Centre, Newcastle University, Newcastle upon Tyne NE1 3BZ, UK"},{"name":"Children\u2019s Hospital of Eastern Ontario Research Institute, University of Ottawa, Ottawa, ON K1H 8L1, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2018,12,17]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"801","DOI":"10.1007\/s00415-014-7490-9","article-title":"Charcot Marie Tooth disease (CMT): Historical perspectives and evolution","volume":"262","author":"Kazamel","year":"2015","journal-title":"J. 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