{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,10]],"date-time":"2026-09-10T05:08:48Z","timestamp":1789016928290,"version":"build-2803163510"},"reference-count":45,"publisher":"MDPI AG","issue":"18","license":[{"start":{"date-parts":[[2026,9,8]],"date-time":"2026-09-08T00:00:00Z","timestamp":1788825600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100001458","name":"American Kennel Club Canine Health Foundation","doi-asserted-by":"publisher","award":["2658"],"award-info":[{"award-number":["2658"]}],"id":[{"id":"10.13039\/100001458","id-type":"DOI","asserted-by":"publisher"}]},{"award":["2658"],"award-info":[{"award-number":["2658"]}],"id":[{"id":"https:\/\/ror.org\/04y3rzk98","id-type":"ROR","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"U.S. National Institutes of Health","doi-asserted-by":"crossref","award":["S10 OD032246"],"award-info":[{"award-number":["S10 OD032246"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"crossref"}]},{"name":"Missouri Spinal Cord Injury\/Disease Research Program"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Animals"],"abstract":"<jats:p>Canine degenerative myelopathy (DM) is a progressive, adult-onset neurodegenerative disease, with similarities to superoxide dismutase 1 (SOD1)-associated ALS. Clinical signs of DM begin with asymmetric pelvic limb general proprioceptive ataxia and spastic paresis that progresses to flaccid tetraplegia and respiratory failure. Although pelvic limb muscle atrophy and peripheral neuropathy have been reported in DM, intramuscular SOD1 accumulation and muscle spindle pathology remain incompletely characterized. This study evaluated pathological changes in the tibialis cranialis muscle of Pembroke Welsh Corgis with early- and late-stage DM and age-matched unaffected controls. Histologic stains and immunohistochemistry were used to evaluate myofiber morphology, fiber type distribution, muscle spindle integrity, and SOD1 immunoreactivity. Compared to unaffected dogs, DM-affected dogs exhibited increased SOD1 immunolabeling, greater variability in myofiber size, altered myofiber shape and packing, and fibrosis. A progressive reduction in the percentage of type I myofibers was observed without evidence of fiber type grouping. These changes were evident during early disease and became more pronounced with disease progression. Muscle spindles exhibited late-stage disruption of intrafusal myofiber organization and marked increase in SOD1 immunoreactivty. The observed alterations suggest that the muscle pathology was, at least in part, intrinsic to the muscle, rather than being secondary to neurodegeneration. Our findings demonstrate early and progressive pathological changes in the tibialis cranialis muscle, expanding our understanding of skeletal muscle involvement in DM.<\/jats:p>","DOI":"10.3390\/ani16182817","type":"journal-article","created":{"date-parts":[[2026,9,8]],"date-time":"2026-09-08T09:02:24Z","timestamp":1788858144000},"page":"2817","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Tibialis Cranialis Extrafusal and Intrafusal Myofibers and Muscle Spindle Pathology in Canine Degenerative Myelopathy"],"prefix":"10.3390","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5560-6005","authenticated-orcid":false,"given":"Brandie","family":"Morgan-Jack","sequence":"first","affiliation":[{"name":"Neurodegenerative Diseases Research Laboratory, Department of Ophthalmology, School of Medicine, University of Missouri, Columbia, MO 65212, USA"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"investigation","vocabulary":"credit"},{"role":"visualization","vocabulary":"credit"},{"role":"methodology","vocabulary":"credit"},{"role":"resources","vocabulary":"credit"},{"role":"project-administration","vocabulary":"credit"},{"role":"funding-acquisition","vocabulary":"credit"},{"role":"formal-analysis","vocabulary":"credit"},{"role":"validation","vocabulary":"credit"},{"role":"writing-review-editing","vocabulary":"credit"},{"role":"writing-original-draft","vocabulary":"credit"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2582-9187","authenticated-orcid":false,"given":"Martin L.","family":"Katz","sequence":"additional","affiliation":[{"name":"Neurodegenerative Diseases Research Laboratory, Department of Ophthalmology, School of Medicine, University of Missouri, Columbia, MO 65212, USA"},{"name":"Department of Veterinary Pathobiology and Integrative Biomedical Sciences, College of Veterinary Medicine, University of Missouri, Columbia, MO 65211, USA"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"conceptualization","vocabulary":"credit"},{"role":"investigation","vocabulary":"credit"},{"role":"visualization","vocabulary":"credit"},{"role":"methodology","vocabulary":"credit"},{"role":"resources","vocabulary":"credit"},{"role":"supervision","vocabulary":"credit"},{"role":"project-administration","vocabulary":"credit"},{"role":"validation","vocabulary":"credit"},{"role":"writing-original-draft","vocabulary":"credit"},{"role":"funding-acquisition","vocabulary":"credit"},{"role":"writing-review-editing","vocabulary":"credit"},{"role":"formal-analysis","vocabulary":"credit"}]},{"given":"Grace R.","family":"Kick","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, School of Medicine Washington University in St. Louis, St. Louis, MO 63110, USA"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"investigation","vocabulary":"credit"},{"role":"validation","vocabulary":"credit"},{"role":"writing-review-editing","vocabulary":"credit"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9267-5528","authenticated-orcid":false,"given":"Joan R.","family":"Coates","sequence":"additional","affiliation":[{"name":"Department of Veterinary Medicine and Surgery, College of Veterinary Medicine, University of Missouri, Columbia, MO 65211, USA"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"conceptualization","vocabulary":"credit"},{"role":"resources","vocabulary":"credit"},{"role":"supervision","vocabulary":"credit"},{"role":"project-administration","vocabulary":"credit"},{"role":"funding-acquisition","vocabulary":"credit"},{"role":"writing-review-editing","vocabulary":"credit"},{"role":"validation","vocabulary":"credit"}]}],"member":"1968","published-online":{"date-parts":[[2026,9,8]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"2794","DOI":"10.1073\/pnas.0812297106","article-title":"Genome-wide association analysis reveals a SOD1 mutation in canine degenerative myelopathy that resembles amyotrophic lateral sclerosis","volume":"106","author":"Awano","year":"2009","journal-title":"Proc. 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