{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,6]],"date-time":"2026-07-06T10:49:45Z","timestamp":1783334985917,"version":"3.54.6"},"reference-count":41,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2023,12,29]],"date-time":"2023-12-29T00:00:00Z","timestamp":1703808000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001691","name":"Japan Society for the Promotion of Science","doi-asserted-by":"publisher","award":["KAKENHI (20K16571)"],"award-info":[{"award-number":["KAKENHI (20K16571)"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Ann Clin Transl Neurol"],"published-print":{"date-parts":[[2024,3]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Objective<\/jats:title><jats:p>Multisystem proteinopathy type 3 (MSP3) is an inherited, pleiotropic degenerative disorder caused by a mutation in heterogeneous nuclear ribonucleoprotein A1 (hnRNPA1), which can affect the muscle, bone, and\/or nervous system. This study aimed to determine detailed histopathological features and transcriptomic profile of <jats:italic>HNRNPA1<\/jats:italic>\u2010mutated skeletal muscles to reveal the core pathomechanism of hereditary inclusion body myopathy (hIBM), a predominant phenotype of MSP3.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Histopathological analyses and RNA sequencing of <jats:italic>HNRNPA1<\/jats:italic>\u2010mutated skeletal muscles harboring a c.940G &gt; A (p.D314N) mutation (NM_031157) were performed, and the results were compared with those of <jats:italic>HNRNPA1<\/jats:italic>\u2010unlinked hIBM and control muscle tissues.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>RNA sequencing revealed aberrant alternative splicing events that predominantly occurred in myofibril components and mitochondrial respiratory complex. Enrichment analyses identified the nuclear pore complex (NPC) and nucleocytoplasmic transport as suppressed pathways. These two pathways were linked by the hub genes <jats:italic>NUP50<\/jats:italic>, <jats:italic>NUP98<\/jats:italic>, <jats:italic>NUP153<\/jats:italic>, <jats:italic>NUP205<\/jats:italic>, and <jats:italic>RanBP2<\/jats:italic>. In immunohistochemistry, these nucleoporin proteins (NUPs) were mislocalized to the cytoplasm and aggregated mostly with TAR DNA\u2010binding protein 43\u2009kDa and, to a lesser extent, with hnRNPA1. Based on ultrastructural observation, irregularly shaped myonuclei with deep invaginations were frequently observed in atrophic fibers, consistent with the disorganization of NPCs. Additionally, regarding the expression profiles of overall NUPs, reduced expression of <jats:italic>NUP98<\/jats:italic>, <jats:italic>NUP153<\/jats:italic>, and <jats:italic>RanBP2<\/jats:italic> was shared with <jats:italic>HNRNPA1<\/jats:italic>\u2010unlinked hIBMs.<\/jats:p><\/jats:sec><jats:sec><jats:title>Interpretation<\/jats:title><jats:p>The shared subset of altered NUPs in amyotrophic lateral sclerosis (ALS), as demonstrated in prior research, <jats:italic>HNRNPA1<\/jats:italic>\u2010mutated, and <jats:italic>HNRNPA1<\/jats:italic>\u2010unlinked hIBM muscle tissues may provide evidence regarding the underlying common nuclear pore pathology of hIBM, ALS, and MSP.<\/jats:p><\/jats:sec>","DOI":"10.1002\/acn3.51977","type":"journal-article","created":{"date-parts":[[2023,12,30]],"date-time":"2023-12-30T06:30:19Z","timestamp":1703917819000},"page":"577-592","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Nuclear pore pathology underlying multisystem proteinopathy type 3\u2010related inclusion body myopathy"],"prefix":"10.1002","volume":"11","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6701-7814","authenticated-orcid":false,"given":"Rumiko","family":"Izumi","sequence":"first","affiliation":[{"name":"Department of Neurology Tohoku University Graduate School of Medicine  Sendai Japan"},{"name":"Department of Medical Genetics Tohoku University Graduate School of Medicine  Sendai Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kensuke","family":"Ikeda","sequence":"additional","affiliation":[{"name":"Department of Neurology Tohoku University Graduate 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