{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,22]],"date-time":"2026-10-22T08:40:25Z","timestamp":1792658425407,"version":"4.5.0"},"reference-count":50,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2026,7,31]],"date-time":"2026-07-31T00:00:00Z","timestamp":1785456000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,7,31]],"date-time":"2026-07-31T00:00:00Z","timestamp":1785456000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Annals of Neurology"],"published-print":{"date-parts":[[2026,11]]},"abstract":"<jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>Repeat expansion mutations underlie diverse neurogenetic disorders, many involving the peripheral nervous system. Despite peripheral neuropathy being the most common neurological disorder worldwide, its contribution to repeat expansion diseases remains poorly defined, and robust preclinical models are limited. We established a translational framework to study peripheral neuropathy in spinocerebellar ataxia type 3 (SCA3), a fatal multisystem disorder caused by a pathogenic CAG expansion in ATXN3.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      SCA3 Knock\u2010In\n                      <jats:italic>Atxn3<\/jats:italic>\n                      <jats:sup>\n                        <jats:italic>Q300\/Q6<\/jats:italic>\n                      <\/jats:sup>\n                      (KI) and\n                      <jats:italic>Atxn3<\/jats:italic>\n                      <jats:sup>\n                        <jats:italic>\u2212\/\u2212<\/jats:italic>\n                      <\/jats:sup>\n                      Knock\u2010Out (KO) mice underwent sensorimotor nerve conduction and behavioral testing. Peripheral tissues were evaluated for SCA3\u2010related pathology, and transcriptional changes in KI dorsal root ganglia (DRG) were assessed by bulk RNA sequencing. To test therapeutic relevance, we generated a conditional \u201cOFF\u201d SCA3 knock\u2010in (cKI) mouse and crossed it with\n                      <jats:italic>Avil\u2010Cre<\/jats:italic>\n                      to selectively silence mutant ATXN3 in sensory neurons. Peripheral phenotyping was repeated in\n                      <jats:italic>Avil\u2010Cre;<\/jats:italic>\n                      cKI mice.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>KI mice developed progressive sensorimotor deficits, peripheral histopathology, and RNA splicing dysregulation that parallel clinical features of SCA3. In contrast, KO mice showed normal peripheral nerve function, implicating toxic gain\u2010of\u2010function from mutant ATXN3 as the causative driver. Sensory neuron\u2013specific silencing of mutant ATXN3 significantly ameliorated peripheral nerve abnormalities and DRG splicing dysregulation.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Interpretation<\/jats:title>\n                    <jats:p>These findings define a pathogenic role for repeat expansion\u2013driven peripheral nerve degeneration in SCA3, identify sensory neurons as key therapeutic targets, and provide a preclinical platform for developing peripheral interventions in SCA3 and related repeat expansion disorders. ANN NEUROL 2026;100:1039\u20131054<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/ana.78317","type":"journal-article","created":{"date-parts":[[2026,8,1]],"date-time":"2026-08-01T04:49:58Z","timestamp":1785559798000},"page":"1039-1054","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Establishing Sensory Neurons as Therapeutic Targets in Peripheral Neuropathy Driven by Polyglutamine Expanded Murine\n                    <scp>ATXN3<\/scp>"],"prefix":"10.1002","volume":"100","author":[{"given":"Juan P.","family":"Mato","sequence":"first","affiliation":[{"name":"Department of Neurology University of Michigan  Ann Arbor MI USA"},{"name":"Neuroscience Graduate Program University of Michigan  Ann Arbor MI USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John M.","family":"Hayes","sequence":"additional","affiliation":[{"name":"Department of Neurology University of Michigan  Ann Arbor MI USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0007-6432-5057","authenticated-orcid":false,"given":"Jacen","family":"Emerson","sequence":"additional","affiliation":[{"name":"Department of Neurology University of Michigan  Ann Arbor MI USA"},{"name":"Neuroscience Graduate Program University of Michigan  Ann Arbor MI USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maeha","family":"Sridharan","sequence":"additional","affiliation":[{"name":"Department of Neurology University of Michigan  Ann Arbor MI USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Toluwani","family":"Adelaja","sequence":"additional","affiliation":[{"name":"Department of Neurology University of Michigan  Ann Arbor MI USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Arsal","family":"Naeem","sequence":"additional","affiliation":[{"name":"Department of Neurology University of Michigan  Ann Arbor MI USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3111-3465","authenticated-orcid":false,"given":"Alexandra F.","family":"Putka","sequence":"additional","affiliation":[{"name":"Department of Neurology University of Michigan  Ann Arbor MI USA"},{"name":"Neuroscience Graduate Program University of Michigan  Ann Arbor MI USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4279-2758","authenticated-orcid":false,"given":"Hayley S.","family":"McLoughlin","sequence":"additional","affiliation":[{"name":"Department of Neurology University of Michigan  Ann Arbor MI USA"},{"name":"Neuroscience Graduate Program University of Michigan  Ann Arbor MI USA"},{"name":"Department of Human Genetics University of Michigan  Ann Arbor MI USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,7,31]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1177\/0883073812448230"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.3389\/fneur.2024.1375218"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12311-015-0684-6"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.3389\/fneur.2020.586610"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00415-024-12753-y"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1136\/practneurol-2020-002822"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1136\/jnnp-2024-333436"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1111\/jns.12451"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa2307952"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13023-021-02040-8"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.trsl.2024.03.009"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.1152\/physrev.00045.2019"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.nbd.2019.104635"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.1002\/ana.25264"},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jns.2011.07.051"},{"key":"e_1_2_9_17_1","doi-asserted-by":"publisher","DOI":"10.1001\/archneur.61.2.257"},{"key":"e_1_2_9_18_1","doi-asserted-by":"publisher","DOI":"10.1111\/ene.15305"},{"key":"e_1_2_9_19_1","doi-asserted-by":"publisher","DOI":"10.1111\/nan.12055"},{"key":"e_1_2_9_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.clinph.2017.09.114"},{"key":"e_1_2_9_21_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12311-024-01769-9"},{"key":"e_1_2_9_22_1","doi-asserted-by":"publisher","DOI":"10.1002\/mus.21396"},{"key":"e_1_2_9_23_1","doi-asserted-by":"publisher","DOI":"10.3390\/cells12040601"},{"key":"e_1_2_9_24_1","doi-asserted-by":"publisher","DOI":"10.1159\/000345274"},{"key":"e_1_2_9_25_1","first-page":"233","volume-title":"Polyglutamine disorders. 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