{"doi":"10.1016/j.ajpath.2025.09.005","title":"The D2.B10-Dmd/J Mouse Model of Duchenne Muscular Dystrophy Exhibits a Severe Mitochondrial Deficiency Not Observed in the C57BL/10ScSn-Dmd/J Mouse","abstract":"Duchenne muscular dystrophy (DMD) is caused by mutations in the DMD gene resulting in dystrophin deficiency in skeletal/cardiac muscle and progressive loss of function. While the genetic causes of DMD have been thoroughly investigated, the energetic consequences have not been well examined across animal models. Previously, the lab examined mitochondrial function across nemaline myopathy mouse models of varying disease severity; here, mitochondrial phenotypes in DMD are assessed through the comparison of the milder C57BL/10ScSn- Dmd mdx /J (B10- mdx ) and the more severe D2.B10- Dmd mdx /J mouse (D2- mdx ) mouse models. D2- mdx exhibit a significant decrease in mitochondrial respiration, undetectable ATP concentrations, increased mitochondrial membrane potential, and alterations in electron transport chain enzyme activities. In contrast, B10- mdx show only mild mitochondrial phenotypes, including decreased ATP content. The D2- mdx mouse has genetic modifiers, including LTBP4 and ANXA6, that have been shown to alter DMD severity in humans. However, these modifiers did not account for mitochondrial differences seen in mdx mice. Both models were treated with a microdystrophin AAV gene therapy to assess whether dystrophin restoration rescued mitochondrial phenotypes. Gene therapy attenuated the ATP deficiency in the B10- mdx mice, but only improved mitochondrial membrane potentials in D2- mdx mice. The exact cause of the D2- mdx mitochondrial phenotypes remains unknown, but secondary disease processes that affect mitochondrial phenotypes should be taken into consideration when choosing an animal model for DMD studies.","journal":"American Journal Of Pathology","year":2025,"id":576477,"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":0,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9348,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2025-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1100749,"name":"J. R. Sutton","orcid":null,"position":1,"is_corresponding":false},{"id":1100290,"name":"Rebecca A. Slick","orcid":"0000-0002-0276-2522","position":2,"is_corresponding":false},{"id":371375,"name":"Hui Meng","orcid":"0000-0002-9864-4183","position":3,"is_corresponding":false},{"id":763052,"name":"Margaret Haberman","orcid":"0000-0002-6714-2295","position":4,"is_corresponding":false},{"id":686770,"name":"Mariah J. Prom","orcid":"0000-0002-6797-9044","position":5,"is_corresponding":false},{"id":315973,"name":"Margaret Beatka","orcid":null,"position":6,"is_corresponding":false},{"id":558983,"name":"Tatyana A. Vetter","orcid":"0000-0002-9904-9140","position":7,"is_corresponding":false},{"id":520960,"name":"Audrey L. Daugherty","orcid":"0009-0005-0182-2238","position":8,"is_corresponding":false},{"id":341893,"name":"Christina A. Pacak","orcid":"0000-0002-7430-124X","position":9,"is_corresponding":false},{"id":300227,"name":"J. Patrick Gonzalez","orcid":null,"position":10,"is_corresponding":false},{"id":371376,"name":"Michael W. Lawlor","orcid":"0000-0003-0731-3950","position":11,"is_corresponding":false},{"id":1107684,"name":"Jennifer A Tinklenberg","orcid":"0000-0002-7895-4950","position":0,"is_corresponding":true}],"reference_count":73,"raw_metadata":null,"created_at":"2026-07-19T02:57:56.636458Z","pmid":"41038271","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":[]}