{"doi":"10.1242/dmm.049006","title":"Extensor carpi ulnaris muscle shows unexpected slow-to-fast fiber-type switch in Duchenne muscular dystrophy dogs","abstract":"Aged dystrophin-null canines are excellent models for studying experimental therapies for Duchenne muscular dystrophy, a lethal muscle disease caused by dystrophin deficiency. To establish the baseline, we studied the extensor carpi ulnaris (ECU) muscle in 15 terminal age (3-year-old) male affected dogs and 15 age/sex-matched normal dogs. Affected dogs showed histological and anatomical hallmarks of dystrophy, including muscle inflammation and fibrosis, myofiber size variation and centralized myonuclei, as well as a significant reduction of muscle weight, muscle-to-body weight ratio and muscle cross-sectional area. To rigorously characterize the contractile properties of the ECU muscle, we developed a novel in situ assay. Twitch and tetanic force, contraction and relaxation rate, and resistance to eccentric contraction-induced force loss were significantly decreased in affected dogs. Intriguingly, the time-to-peak tension and half-relaxation time were significantly shortened in affected dogs. Contractile kinetics predicted an unforeseen slow-to-fast myofiber-type switch, which we confirmed at the protein and transcript level. Our study establishes a foundation for studying long-term and late-stage therapeutic interventions in dystrophic canines. The unexpected myofiber-type switch highlights the complexity of muscle remodeling in dystrophic large mammals. This article has an associated First Person interview with the first author of the paper.","journal":"Disease Models & Mechanisms","year":2021,"id":189468,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":15,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9543,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2021-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":10742,"name":"H. T. Yang","orcid":"0000-0003-3554-7113","position":1,"is_corresponding":false},{"id":752123,"name":"Matthew J. Burke","orcid":"0000-0002-9112-5452","position":2,"is_corresponding":false},{"id":625985,"name":"James Teixeira","orcid":"0000-0002-0618-2605","position":3,"is_corresponding":false},{"id":658767,"name":"Gregory J. Jenkins","orcid":"0000-0002-5440-6570","position":4,"is_corresponding":false},{"id":333617,"name":"N. Nora Yang","orcid":"0000-0001-7245-8035","position":5,"is_corresponding":false},{"id":580505,"name":"Gang Yao","orcid":"0000-0002-2763-8667","position":6,"is_corresponding":false},{"id":320631,"name":"Dongsheng Duan","orcid":"0000-0003-4109-1132","position":7,"is_corresponding":false},{"id":333615,"name":"Chady H. Hakim","orcid":"0000-0001-6865-050X","position":0,"is_corresponding":true}],"reference_count":55,"raw_metadata":null,"created_at":"2026-07-18T23:49:18.604374Z","pmid":"34704592","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}