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Although previous studies determined multiple roles for SETBP1 and its associated pathways in disease manifestation, they did not assess whether cell-type-specific alternative splicing (AS) plays a role in SGS. We quantified gene and splice junction expression from single-nuclei RNA-sequencing data from the cerebral cortex and kidney of atypical Setbp1S858R SGS patient variant and wild-type mice. We identified 33 and 62 genes with statistically significant alterations in splice junction usage in the brain and kidney, respectively. We identified significant splice junction usage in a member of the heterogeneous nuclear ribonucleoprotein family, Hnrnpa2b1. These findings were cell-type specific in the cerebral cortex and cell-type agnostic in the kidney, suggesting tissue specificity of AS in Setbp1S858R mice. To broaden the impact of our results for the rare disease community, we developed a point-and-click web application that enables users to explore single-cell-resolution changes at the gene and splice junction levels. Overall, our findings implicate AS in a tissue- and cell-type-specific manner in the cerebral cortex and kidney of Setbp1S858R mice.<\/jats:p>","DOI":"10.1242\/dmm.052402","type":"journal-article","created":{"date-parts":[[2026,2,27]],"date-time":"2026-02-27T11:22:31Z","timestamp":1772191351000},"source":"Crossref","is-referenced-by-count":1,"title":["Cell-type-specific alternative splicing in the brain and kidney of a\n                    <i>Setbp1<\/i>\n                    S858R Schinzel\u2013Giedion syndrome mouse"],"prefix":"10.1242","volume":"19","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1654-4240","authenticated-orcid":false,"given":"Tabea M.","family":"Soelter","sequence":"first","affiliation":[{"name":"Heersink School of Medicine, The University of Alabama at Birmingham Department of Cell, Developmental and Integrative Biology , , Birmingham, AL 35294 ,","place":["USA"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4244-1456","authenticated-orcid":false,"given":"Emma F.","family":"Jones","sequence":"additional","affiliation":[{"name":"Heersink School of Medicine, The University of Alabama at Birmingham Department of Cell, Developmental and Integrative Biology , , Birmingham, AL 35294 ,","place":["USA"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9423-0135","authenticated-orcid":false,"given":"Timothy C.","family":"Howton","sequence":"additional","affiliation":[{"name":"Heersink School of Medicine, The University of Alabama at Birmingham Department of Cell, Developmental and Integrative Biology , , Birmingham, AL 35294 ,","place":["USA"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0004-7347-4722","authenticated-orcid":false,"given":"Anthony B.","family":"Crumley","sequence":"additional","affiliation":[{"name":"Heersink School of Medicine, The University of Alabama at Birmingham Department of Cell, Developmental and Integrative Biology , , Birmingham, AL 35294 ,","place":["USA"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7078-1215","authenticated-orcid":false,"given":"Elizabeth J.","family":"Wilk","sequence":"additional","affiliation":[{"name":"Heersink School of Medicine, The University of Alabama at Birmingham Department of Cell, Developmental and Integrative Biology , , Birmingham, AL 35294 ,","place":["USA"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1642-8904","authenticated-orcid":false,"given":"Brittany N.","family":"Lasseigne","sequence":"additional","affiliation":[{"name":"Heersink School of Medicine, The University of Alabama at Birmingham Department of Cell, Developmental and Integrative Biology , , Birmingham, AL 35294 ,","place":["USA"]}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"237","published-online":{"date-parts":[[2026,2,27]]},"reference":[{"key":"2026022706222640700_DMM052402C1","doi-asserted-by":"publisher","first-page":"36","DOI":"10.1186\/2040-2392-4-36","article-title":"SFARI Gene 2.0: a community-driven knowledgebase for the autism spectrum disorders (ASDs)","volume":"4","author":"Abrahams","year":"2013","journal-title":"Mol. 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