{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T09:27:24Z","timestamp":1785403644489,"version":"3.56.0"},"posted":{"date-parts":[[2025,5,29]]},"group-title":"Neuroscience","reference-count":43,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2025,5,29]],"date-time":"2025-05-29T00:00:00Z","timestamp":1748476800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"award":["R21NS126845"],"award-info":[{"award-number":["R21NS126845"]}],"id":[{"id":"https:\/\/ror.org\/01s5ya894","id-type":"ROR","asserted-by":"publisher"}]},{"award":["R01NS121130"],"award-info":[{"award-number":["R01NS121130"]}],"id":[{"id":"https:\/\/ror.org\/01s5ya894","id-type":"ROR","asserted-by":"publisher"}]},{"award":["T32NS115705"],"award-info":[{"award-number":["T32NS115705"]}],"id":[{"id":"https:\/\/ror.org\/01s5ya894","id-type":"ROR","asserted-by":"publisher"}]},{"award":["HD103536"],"award-info":[{"award-number":["HD103536"]}],"id":[{"id":"https:\/\/ror.org\/04byxyr05","id-type":"ROR","asserted-by":"publisher"}]},{"name":"Harry T. Mangurian Jr. Foundation"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2025,5,29]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                <jats:p>\n                  Sez6L2 autoantibodies have been reported in patients with subacute cerebellar ataxia, presenting with gait disturbances, frequent falls, slurred speech, and repetitive eye movements. These case studies suggest that autoimmunity against Sez6L2 causes cerebellar damage leading to ataxia. Sez6L2 is a transmembrane protein expressed by most neurons, with the highest levels in the cerebellum. We tested whether immunizing C57BL\/6 mice against Sez6L2 could produce an autoimmune response resulting in ataxia symptoms and immune attack on the brain\/cerebellum. We found that immunized mice generated significant levels of anti-Sez6L2 antibodies, with IgGs present in the cerebellar parenchyma. Additionally, Sez6L2-immunized mice developed a significant population of Sez6L2-specific T cells targeting two immunodominant epitopes and showed increased CD4\n                  <jats:sup>+<\/jats:sup>\n                  T cell infiltration into the brain. These mice exhibited mild mobility impairments in open field, wire grid walk, and pole test assays. Our results indicate that an autoimmune response to Sez6L2 in mice can lead to mobility impairments and pathology consistent with human cerebellar ataxia associated with Sez6L2 autoantibodies. This new mouse model should be useful for mechanistic studies on this poorly understood autoimmune disease and for pre-clinical testing of therapeutic strategies targeting the immune system in patients with Sez6L2 antibodies.\n                <\/jats:p>","DOI":"10.1101\/2025.05.28.656724","type":"posted-content","created":{"date-parts":[[2025,5,29]],"date-time":"2025-05-29T10:10:13Z","timestamp":1748513413000},"source":"Crossref","is-referenced-by-count":1,"title":["Sez6L2 autoimmunity induces cerebellar ataxia in mice"],"prefix":"10.64898","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1580-3853","authenticated-orcid":false,"given":"Carlos J.","family":"Reyes-Sep\u00falveda","sequence":"first","affiliation":[{"name":"Immunology, Microbiology, and Virology Graduate Program, University of Rochester Medical Center, Rochester, NY"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-8524-2430","authenticated-orcid":false,"given":"Julia","family":"Granato","sequence":"additional","affiliation":[{"name":"Neuroscience Graduate Program, University of Rochester Medical Center, Rochester, NY"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John","family":"Randolph","sequence":"additional","affiliation":[{"name":"Department of Neurology, University of Rochester Medical Center, Rochester, NY"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Allison T.","family":"Ryan","sequence":"additional","affiliation":[{"name":"Immunology, Microbiology, and Virology Graduate Program, University of Rochester Medical Center, Rochester, NY"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alison","family":"Hobbins","sequence":"additional","affiliation":[{"name":"Department of Neurology, University of Rochester Medical Center, Rochester, NY"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0327-5259","authenticated-orcid":false,"given":"Angela","family":"Stout","sequence":"additional","affiliation":[{"name":"Department of Neurology, University of Rochester Medical Center, Rochester, NY"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2471-8562","authenticated-orcid":false,"given":"Herman","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Neurology, University of Rochester Medical Center, Rochester, NY"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3949-1594","authenticated-orcid":false,"given":"Jennetta W.","family":"Hammond","sequence":"additional","affiliation":[{"name":"Department of Neurology, University of Rochester Medical Center, Rochester, NY"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"54368","reference":[{"key":"2026041123561558000_2025.05.28.656724v1.1","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-021-03220-z"},{"key":"2026041123561558000_2025.05.28.656724v1.2","doi-asserted-by":"crossref","unstructured":"Garza M , Piquet AL . 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