{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,8]],"date-time":"2026-01-08T16:47:05Z","timestamp":1767890825964,"version":"3.49.0"},"reference-count":111,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2023,6,25]],"date-time":"2023-06-25T00:00:00Z","timestamp":1687651200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"FSHD society"},{"name":"FSHD Global Research Foundation"},{"name":"Muscular Dystrophy Association"},{"name":"Friends of FSH Research"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JPM"],"abstract":"<jats:p>Facioscapulohumeral muscular dystrophy (FSHD) is caused by the aberrant expression of the double homeobox 4 (DUX4) gene. The FLExDUX4 mouse model carries an inverted human DUX4 transgene which has leaky DUX4 transgene expression at a very low level. No overt muscle pathology was reported before 16 weeks. The purpose of this study is to track and characterize the FLExDUX4 phenotypes for a longer period, up to one year old. In addition, transcriptomic changes in the muscles of 2-month-old mice were investigated using RNA-seq. The results showed that male FLExDUX4 mice developed more severe phenotypes and at a younger age in comparison to the female mice. These include lower body and muscle weight, and muscle weakness measured by grip strength measurements. Muscle pathological changes were observed at older ages, including fibrosis, decreased size of type IIa and IIx myofibers, and the development of aggregates containing TDP-43 in type IIb myofibers. Muscle transcriptomic data identified early molecular changes in biological pathways regulating circadian rhythm and adipogenesis. The study suggests a slow progressive change in molecular and muscle phenotypes in response to the low level of DUX4 expression in the FLExDUX4 mice.<\/jats:p>","DOI":"10.3390\/jpm13071040","type":"journal-article","created":{"date-parts":[[2023,6,26]],"date-time":"2023-06-26T01:42:32Z","timestamp":1687743752000},"page":"1040","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Molecular and Phenotypic Changes in FLExDUX4 Mice"],"prefix":"10.3390","volume":"13","author":[{"given":"Kelly","family":"Murphy","sequence":"first","affiliation":[{"name":"Institute for Biomedical Sciences, The George Washington University, Washington, DC 20037, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Aiping","family":"Zhang","sequence":"additional","affiliation":[{"name":"Center for Genetic Medicine Research, Children\u2019s National Hospital, Washington, DC 20010, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2134-418X","authenticated-orcid":false,"given":"Adam J.","family":"Bittel","sequence":"additional","affiliation":[{"name":"Center for Genetic Medicine Research, Children\u2019s National Hospital, Washington, DC 20010, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yi-Wen","family":"Chen","sequence":"additional","affiliation":[{"name":"Institute for Biomedical Sciences, The George Washington University, Washington, DC 20037, USA"},{"name":"Center for Genetic Medicine Research, Children\u2019s National Hospital, Washington, DC 20010, USA"},{"name":"Department of Genomics and Precision Medicine, School of Medicine and Health Science, The George Washington University, Washington, DC 20037, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2023,6,25]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1002\/mus.20522","article-title":"Facioscapulohumeral muscular dystrophy","volume":"34","author":"Tawil","year":"2006","journal-title":"Muscle Nerve"},{"key":"ref_2","first-page":"1916","article-title":"Facioscapulohumeral Muscular Dystrophy","volume":"22","author":"Statland","year":"2016","journal-title":"Continuum"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"512","DOI":"10.1002\/mus.24569","article-title":"Whole-body magnetic resonance imaging evaluation of facioscapulohumeral muscular dystrophy","volume":"52","author":"Leung","year":"2015","journal-title":"Muscle Nerve"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"1056","DOI":"10.1212\/WNL.0000000000000797","article-title":"Population-based incidence and prevalence of facioscapulohumeral dystrophy","volume":"83","author":"Deenen","year":"2014","journal-title":"Neurology"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"525","DOI":"10.1016\/S0960-8966(01)00201-2","article-title":"Genetic characterization of a large, historically significant Utah kindred with facioscapulohumeral dystrophy","volume":"11","author":"Flanigan","year":"2001","journal-title":"Neuromuscul. 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