{"doi":"10.3390/ijms231810841","title":"Myofibrillar Lattice Remodeling Is a Structural Cytoskeletal Predictor of Diaphragm Muscle Weakness in a Fibrotic mdx (mdx Cmah−/−) Model","abstract":"Duchenne muscular dystrophy (DMD) is a degenerative genetic myopathy characterized by complete absence of dystrophin. Although the mdx mouse lacks dystrophin, its phenotype is milder compared to DMD patients. The incorporation of a null mutation in the Cmah gene led to a more DMD-like phenotype (i.e., more fibrosis). Although fibrosis is thought to be the major determinant of ‘structural weakness’, intracellular remodeling of myofibrillar geometry was shown to be a major cellular determinant thereof. To dissect the respective contribution to muscle weakness, we assessed biomechanics and extra- and intracellular architecture of whole muscle and single fibers from extensor digitorum longus (EDL) and diaphragm. Despite increased collagen contents in both muscles, passive stiffness in mdx Cmah−/− diaphragm was similar to wt mice (EDL muscles were twice as stiff). Isometric twitch and tetanic stresses were 50% reduced in mdx Cmah−/− diaphragm (15% in EDL). Myofibrillar architecture was severely compromised in mdx Cmah−/− single fibers of both muscle types, but more pronounced in diaphragm. Our results show that the mdx Cmah−/− genotype reproduces DMD-like fibrosis but is not associated with changes in passive visco-elastic muscle stiffness. Furthermore, detriments in active isometric force are compatible with the pronounced myofibrillar disarray of the dystrophic background.","journal":"International Journal of Molecular Sciences","year":2022,"id":282702,"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":7,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9537,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2022-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":959129,"name":"Stefanie Nübler","orcid":null,"position":1,"is_corresponding":false},{"id":914126,"name":"Andreas Buttgereit","orcid":"0000-0002-5065-5430","position":2,"is_corresponding":false},{"id":288084,"name":"Lucas Smith","orcid":"0000-0002-7610-4231","position":3,"is_corresponding":false},{"id":824043,"name":"Alexander Mühlberg","orcid":"0000-0001-8039-844X","position":4,"is_corresponding":false},{"id":958698,"name":"Julian Bauer","orcid":"0000-0002-2149-1094","position":5,"is_corresponding":false},{"id":958699,"name":"Mena Michael","orcid":"0000-0003-4805-0333","position":6,"is_corresponding":false},{"id":958700,"name":"Lucas Kreiß","orcid":"0000-0002-7749-0015","position":7,"is_corresponding":false},{"id":958701,"name":"Michael Haug","orcid":"0000-0001-5968-2593","position":8,"is_corresponding":false},{"id":260624,"name":"Elisabeth R. Barton","orcid":"0000-0002-7401-4398","position":9,"is_corresponding":false},{"id":323045,"name":"Oliver Friedrich","orcid":"0000-0003-2238-2049","position":10,"is_corresponding":false},{"id":958697,"name":"Paul Ritter","orcid":"0000-0001-9227-8031","position":0,"is_corresponding":true}],"reference_count":37,"raw_metadata":null,"created_at":"2026-07-19T00:29:19.691592Z","pmid":"36142754","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":[]}