{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T14:26:12Z","timestamp":1790778372009,"version":"4.1.0"},"reference-count":40,"publisher":"American Society for Clinical Investigation","issue":"9","license":[{"start":{"date-parts":[[2024,5,8]],"date-time":"2024-05-08T00:00:00Z","timestamp":1715126400000},"content-version":"vor","delay-in-days":48,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"NIH","award":["R01NS022920 (H.T.O.),R35NS127248 (H.T.O.),R01AR049899 (J.M.E.),R01NS049206 (V.C.W.)"],"award-info":[{"award-number":["R01NS022920 (H.T.O.),R35NS127248 (H.T.O.),R01AR049899 (J.M.E.),R01NS049206 (V.C.W.)"]}]},{"name":"NIH","award":["R01NS027699 (H.Y.Z.)."],"award-info":[{"award-number":["R01NS027699 (H.Y.Z.)."]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2024,5,8]]},"abstract":"<jats:p>\n                    Spinocerebellar ataxia type 1 (SCA1) is a fatal neurodegenerative disease caused by an expanded polyglutamine tract in the widely expressed ataxin-1 (ATXN1) protein. To elucidate anatomical regions and cell types that underlie mutant ATXN1-induced disease phenotypes, we developed a floxed conditional knockin mouse (\n                    <jats:italic>\n                      f-ATXN1\n                      <jats:sup>146Q\/2Q<\/jats:sup>\n                    <\/jats:italic>\n                    ) with mouse\n                    <jats:italic>Atxn1<\/jats:italic>\n                    coding exons replaced by human\n                    <jats:italic>ATXN1<\/jats:italic>\n                    exons encoding 146 glutamines.\n                    <jats:italic>\n                      f-ATXN1\n                      <jats:sup>146Q\/2Q<\/jats:sup>\n                    <\/jats:italic>\n                    mice manifested SCA1-like phenotypes including motor and cognitive deficits, wasting, and decreased survival. Central nervous system (CNS) contributions to disease were revealed using\n                    <jats:italic>\n                      f-ATXN1\n                      <jats:sup>146Q\/2Q<\/jats:sup>\n                    <\/jats:italic>\n                    ;\n                    <jats:italic>Nestin-Cre<\/jats:italic>\n                    mice, which showed improved rotarod, open field, and Barnes maze performance by 6\u201312 weeks of age. In contrast, striatal contributions to motor deficits using\n                    <jats:italic>\n                      f-ATXN1\n                      <jats:sup>146Q\/2Q<\/jats:sup>\n                    <\/jats:italic>\n                    ;\n                    <jats:italic>Rgs9-Cre<\/jats:italic>\n                    mice revealed that mice lacking\n                    <jats:italic>\n                      ATXN1\n                      <jats:sup>146Q\/2Q<\/jats:sup>\n                    <\/jats:italic>\n                    in striatal medium-spiny neurons showed a trending improvement in rotarod performance at 30 weeks of age. Surprisingly, a prominent role for muscle contributions to disease was revealed in\n                    <jats:italic>\n                      f-ATXN1\n                      <jats:sup>146Q\/2Q<\/jats:sup>\n                    <\/jats:italic>\n                    ;\n                    <jats:italic>ACTA1-Cre<\/jats:italic>\n                    mice based on their recovery from kyphosis and absence of muscle pathology. Collectively, data from the targeted conditional deletion of the expanded allele demonstrated CNS and peripheral contributions to disease and highlighted the need to consider muscle in addition to the brain for optimal SCA1 therapeutics.\n                  <\/jats:p>","DOI":"10.1172\/jci.insight.176057","type":"journal-article","created":{"date-parts":[[2024,3,21]],"date-time":"2024-03-21T12:00:51Z","timestamp":1711022451000},"source":"Crossref","is-referenced-by-count":15,"title":["Mapping SCA1 regional vulnerabilities reveals neural and skeletal muscle contributions to disease"],"prefix":"10.1172","volume":"9","author":[{"given":"Lisa","family":"Duvick","sequence":"first","affiliation":[{"name":"Institute of Translational Neuroscience,"},{"name":"Department of Laboratory Medicine and Pathology, and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"W. 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