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Sarco\/endoplasmic reticulum calcium ATPase (SERCA), a key regulator of cytosolic calcium levels, exhibits reduced activity in animal models of DMD and human patients. Dwarf open reading frame (DWORF), a positive SERCA regulator, is downregulated in mdx DMD mice, and adeno-associated virus-mediated DWORF overexpression has been shown to ameliorate DMD cardiomyopathy. The canine DMD model provides a crucial bridge for translating findings from mice to humans. To investigate DWORF expression in this model, we developed a canine-specific anti-DWORF antibody, as the existing murine antibody is ineffective. This antibody detected DWORF in human, pig, cat and rabbit muscle, but not in mouse muscle. DWORF was absent in muscle tissues of neonatal normal dogs but highly expressed in those of adult dogs. In DMD-affected dogs aged 8 months or older, DWORF expression was significantly reduced in both cardiac and skeletal muscle. This study establishes a foundation for evaluating DWORF-based gene therapy in the canine DMD model, advancing the potential for clinical translation.<\/jats:p>","DOI":"10.1242\/dmm.052285","type":"journal-article","created":{"date-parts":[[2025,6,25]],"date-time":"2025-06-25T10:52:42Z","timestamp":1750848762000},"source":"Crossref","is-referenced-by-count":3,"title":["DWORF expression is reduced in a large animal model of Duchenne muscular dystrophy"],"prefix":"10.1242","volume":"18","author":[{"given":"Aaron M.","family":"Gibson","sequence":"first","affiliation":[{"name":"The Heart Institute 1 , Division of Molecular Cardiovascular Biology , , Cincinnati, OH 45229 ,","place":["USA"]},{"name":"Cincinnati Children's Hospital Medical Center 1 , Division of Molecular Cardiovascular Biology , , Cincinnati, OH 45229 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiufang","family":"Pan","sequence":"additional","affiliation":[{"name":"School of Medicine, 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