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Nuclear Factor Erythroid 2\u2010Related Factor 2 (NRF2) is a critical redox rheostat that regulates oxidative stress responses, and its deletion is known to accelerate muscle atrophy and weakness during aging (sarcopenia) or denervation. Conversely, pharmacologic activation of NRF2 extends mouse lifespan and attenuates sarcopenia. Similarly, deletion of Kelch\u2010like ECH\u2010associated Protein 1 (Keap1), a negative regulator of NRF2, enhances exercise capacity. The purpose of this study was to determine whether muscle\u2010specific Keap1 deletion is sufficient to prevent muscle atrophy and weakness in mice following 7\u2009days of hindlimb unloading (HU). To test this hypothesis, control (Ctrl) and tamoxifen\u2010inducible, muscle\u2010specific Keap1 knockout (mKO) mice were subjected to either normal housing (Sham) or HU for 7\u2009days. Activation of NRF2 in muscle was confirmed by increased mRNA of NRF2 targets thioredoxin 1 (Txn1) and NAD(P)H quinone dehydrogenase 1 (NQO1) in mKO mice. Keap1 deletion had an effect to increase force\u2010generating capacity at baseline. However, muscle masses, cross\u2010sectional area, and ex\u00a0vivo force were not different between mKO and Ctrl HU mice. In addition, muscle 4\u2010hydroxynonenal\u2010modified proteins and protein carbonyls were unaffected by Keap1 deletion. These data suggest that NRF2 activation improves muscle force production during ambulatory conditions but is not sufficient to prevent muscle atrophy or weakness following 7\u2009days of HU.<\/jats:p>","DOI":"10.1096\/fj.202402810r","type":"journal-article","created":{"date-parts":[[2025,3,14]],"date-time":"2025-03-14T11:48:31Z","timestamp":1741952911000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Muscle\u2010specific Keap1 deletion enhances force production but does not prevent inactivity\u2010induced muscle atrophy in mice"],"prefix":"10.1096","volume":"39","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2370-4118","authenticated-orcid":false,"given":"Edwin R.","family":"Miranda","sequence":"first","affiliation":[{"name":"Diabetes &amp; Metabolism Research Center University of Utah  Salt Lake City Utah USA"},{"name":"Department of Nutrition and Integrative Physiology University of Utah  Salt Lake City 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