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Studies have reported decreased expression of dystrophin in atrophying muscles during wasting conditions, and that restoration of dystrophin can attenuate atrophy, suggesting a role in maintaining muscle mass. Phosphorylation of S3059 within the cysteine\u2010rich region of dystrophin enhances binding between dystrophin and \u03b2\u2010dystroglycan, and mimicking phosphorylation at this site by site\u2010directed mutagenesis attenuates myotube atrophy in\u00a0vitro. To determine whether dystrophin phosphorylation can attenuate muscle wasting in\u00a0vivo, CRISPR\u2010Cas9 was used to generate mice with whole body mutations of S3059 to either alanine (DmdS3059A) or glutamate (DmdS3059E), to mimic a loss of, or constitutive phosphorylation of S3059, on all endogenous dystrophin isoforms, respectively. Sciatic nerve transection was performed on these mice to determine whether phosphorylation of dystrophin S3059 could attenuate denervation atrophy. At 14\u2009days post denervation, atrophy of tibialis anterior (TA) but not gastrocnemius or soleus muscles, was partially attenuated in DmdS3059E mice relative to WT mice. Attenuation of atrophy was associated with increased expression of \u03b2\u2010dystroglycan in TA muscles of DmdS3059E mice. Dystrophin S3059 phosphorylation can partially attenuate denervation\u2010induced atrophy, but may have more significant impact in less severe modes of muscle wasting.<\/jats:p>","DOI":"10.14814\/phy2.16145","type":"journal-article","created":{"date-parts":[[2024,7,13]],"date-time":"2024-07-13T05:29:05Z","timestamp":1720848545000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Dystrophin S3059 phosphorylation partially attenuates denervation atrophy in mouse tibialis anterior muscles"],"prefix":"10.14814","volume":"12","author":[{"given":"Kristy","family":"Swiderski","sequence":"first","affiliation":[{"name":"Department of Anatomy and Physiology, Centre for Muscle Research The University of Melbourne  Melbourne Victoria Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Timur","family":"Naim","sequence":"additional","affiliation":[{"name":"Department of Anatomy and Physiology, Centre for 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