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The disease-causing protein ataxin-1 is fairly ubiquitously expressed throughout the brain and spinal cord, but most studies have primarily focused on the role of ataxin-1 in the cerebellum and brainstem. Therefore, the functions of ataxin-1 and the effects of SCA1 mutations in other brain regions including the cortex are not well-known. Here, we characterized pathology in the motor cortex of a SCA1 mouse model and performed RNA sequencing in this brain region to investigate the impact of mutant ataxin-1 towards transcriptomic alterations. We identified progressive cortical pathology and significant transcriptomic changes in the motor cortex of a SCA1 mouse model. We also identified progressive, region-specific, colocalization of p62 protein with mutant ataxin-1 aggregates in broad brain regions, but not the cerebellum or brainstem. A cross-regional comparison of the SCA1 cortical and cerebellar transcriptomic changes identified both common and unique gene expression changes between the two regions, including shared synaptic dysfunction and region-specific kinase regulation. These findings suggest that the cortex is progressively impacted via both shared and region-specific mechanisms in SCA1.<\/jats:p>","DOI":"10.3390\/cells11172632","type":"journal-article","created":{"date-parts":[[2022,8,24]],"date-time":"2022-08-24T21:03:51Z","timestamp":1661375031000},"page":"2632","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Identifying Disease Signatures in the Spinocerebellar Ataxia Type 1 Mouse Cortex"],"prefix":"10.3390","volume":"11","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8642-6640","authenticated-orcid":false,"given":"Kimberly","family":"Luttik","sequence":"first","affiliation":[{"name":"Interdepartmental Neuroscience Program, Yale School of Medicine, New Haven, CT 06510, USA"},{"name":"Department of Neuroscience, Yale School of Medicine, New Haven, CT 06510, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Victor","family":"Olmos","sequence":"additional","affiliation":[{"name":"Department of Genetics, Yale School of Medicine, New Haven, CT 06510, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ashley","family":"Owens","sequence":"additional","affiliation":[{"name":"Interdepartmental Neuroscience Program, Yale School of Medicine, New Haven, CT 06510, USA"},{"name":"Department of Neuroscience, Yale School of Medicine, New Haven, CT 06510, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Aryaan","family":"Khan","sequence":"additional","affiliation":[{"name":"Yale College, New Haven, CT 06510, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3889-3284","authenticated-orcid":false,"given":"Joy","family":"Yun","sequence":"additional","affiliation":[{"name":"Yale College, New Haven, CT 06510, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Terri","family":"Driessen","sequence":"additional","affiliation":[{"name":"Department of Genetics, Yale School of Medicine, New Haven, CT 06510, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Janghoo","family":"Lim","sequence":"additional","affiliation":[{"name":"Interdepartmental Neuroscience Program, Yale School of Medicine, New Haven, CT 06510, USA"},{"name":"Department of Neuroscience, Yale School of Medicine, New Haven, CT 06510, USA"},{"name":"Department of Genetics, Yale School of Medicine, New Haven, CT 06510, USA"},{"name":"Program in Cellular Neuroscience, Neurodegeneration and Repair, Yale School of Medicine, New Haven, CT 06510, USA"},{"name":"Yale Stem Cell Center, Yale School of Medicine, New Haven, CT 06510, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2022,8,24]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"575","DOI":"10.1146\/annurev.neuro.29.051605.113042","article-title":"Trinucleotide Repeat Disorders","volume":"30","author":"Orr","year":"2007","journal-title":"Annu. 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