{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,8]],"date-time":"2026-09-08T21:16:55Z","timestamp":1788902215563,"version":"build-2803163510"},"reference-count":59,"publisher":"Wiley","issue":"10","license":[{"start":{"date-parts":[[2021,9,21]],"date-time":"2021-09-21T00:00:00Z","timestamp":1632182400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100011596","name":"Conselleria d'Educaci\u00f3, Investigaci\u00f3, Cultura i Esport","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100011596","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["faseb.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The FASEB Journal"],"published-print":{"date-parts":[[2021,10]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    Limb\u2010girdle muscular dystrophy D2 (LGMDD2) is an ultrarare autosomal dominant myopathy caused by mutation of the normal stop codon of the\n                    <jats:italic>TNPO3<\/jats:italic>\n                    nuclear importin. The mutant protein carries a 15 amino acid C\u2010terminal extension associated with pathogenicity. Here we report the first animal model of the disease by expressing the human mutant\n                    <jats:italic>TNPO3<\/jats:italic>\n                    gene in\n                    <jats:italic>Drosophila<\/jats:italic>\n                    musculature or motor neurons and concomitantly silencing the endogenous expression of the fly protein ortholog. A similar genotype expressing wildtype\n                    <jats:italic>TNPO3<\/jats:italic>\n                    served as a control. Phenotypes characterization revealed that mutant\n                    <jats:italic>TNPO3<\/jats:italic>\n                    expression targeted at muscles or motor neurons caused LGMDD2\u2010like phenotypes such as muscle degeneration and atrophy, and reduced locomotor ability. Notably, LGMDD2 mutation increase TNPO3 at the transcript and protein level in the\n                    <jats:italic>Drosophila<\/jats:italic>\n                    model Upregulated muscle autophagy observed in LGMDD2 patients was also confirmed in the fly model, in which the anti\u2010autophagic drug chloroquine was able to rescue histologic and functional phenotypes. Overall, we provide a proof of concept of autophagy as a target to treat disease phenotypes and propose a neurogenic component to explain mutant TNPO3 pathogenicity in diseased muscles.\n                  <\/jats:p>","DOI":"10.1096\/fj.202100539rr","type":"journal-article","created":{"date-parts":[[2021,9,21]],"date-time":"2021-09-21T14:47:25Z","timestamp":1632235645000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":16,"title":["Inhibition of autophagy rescues muscle atrophy in a LGMDD2\n                    <i>Drosophila<\/i>\n                    model"],"prefix":"10.1096","volume":"35","author":[{"given":"\u00c1gueda","family":"Bl\u00e1zquez\u2010Bernal","sequence":"first","affiliation":[{"name":"Translational Genomics Group University Institute for Biotechnology and Biomedicine (BIOTECMED) University of Valencia Valencia Spain"},{"name":"Area of Metabolism and Organic Failure Incliva Health Research Institute Valencia 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