{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,23]],"date-time":"2026-04-23T04:00:24Z","timestamp":1776916824735,"version":"3.51.2"},"reference-count":82,"publisher":"MDPI AG","issue":"21","license":[{"start":{"date-parts":[[2025,10,23]],"date-time":"2025-10-23T00:00:00Z","timestamp":1761177600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000025","name":"National Institute of Mental Health","doi-asserted-by":"crossref","award":["R01MH115958"],"award-info":[{"award-number":["R01MH115958"]}],"id":[{"id":"10.13039\/100000025","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100008771","name":"Tourette Association of America","doi-asserted-by":"crossref","id":[{"id":"10.13039\/100008771","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100000065","name":"National Institute of Neurological Disorders and Stroke","doi-asserted-by":"crossref","id":[{"id":"10.13039\/100000065","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100000867","name":"Robert Wood Johnson Foundation","doi-asserted-by":"crossref","award":["#74260"],"award-info":[{"award-number":["#74260"]}],"id":[{"id":"10.13039\/100000867","id-type":"DOI","asserted-by":"crossref"}]},{"name":"New Jersey Center for Tourette Syndrome"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Tourette Disorder (TD) is a prevalent neurodevelopmental condition characterized by chronic motor and vocal tics. A mechanistic understanding of both the genetic etiology and brain pathophysiology remains poor. To gain insight into the molecular underpinnings of TD, we have generated a novel mouse model expressing an orthologous human mutation in CELSR3, a high-confidence TD risk gene. This putative damaging de novo variant, R774H, causes an amino acid substitution within the fifth cadherin repeat. Unlike previous Celsr3 TD models and Celsr3 constitutive null mice, mice homozygous for the R774H amino acid substitution are viable. They have grossly normal forebrain development and no changes to the density of cortical and striatal interneuron subpopulations. However, 3D geometric analysis of cortical pyramidal neurons revealed changes to dendritic patterning and the types and distributions of spines. Furthermore, patch clamp recordings in cholinergic interneurons located within the sensorimotor striatum uncovered mild intrinsic hyperexcitability and changes to spine density. Despite these changes, Celsr3R774H homozygous mice do not show repetitive motor behaviors at baseline nor motor learning impairments. However, Celsr3R774H homozygous males have sensorimotor gating deficits, a behavioral phenotype observed in both humans with TD and previously reported mouse models. Our findings suggest human mutations in CELSR3 may affect dendritic patterning, spine formation and\/or turnover, and the firing properties of neurons within cortico-striatal circuits.<\/jats:p>","DOI":"10.3390\/ijms262110307","type":"journal-article","created":{"date-parts":[[2025,10,23]],"date-time":"2025-10-23T09:44:30Z","timestamp":1761212670000},"page":"10307","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["A Celsr3 Mutation Linked to Tourette Disorder Disrupts Cortical Dendritic Patterning and Striatal Cholinergic Interneuron Excitability"],"prefix":"10.3390","volume":"26","author":[{"ORCID":"https:\/\/orcid.org\/0009-0001-0419-1233","authenticated-orcid":false,"given":"Cara","family":"Nasello","sequence":"first","affiliation":[{"name":"Department of Cell Biology and Neuroscience, Rutgers, The State University of New Jersey, Piscataway, NJ 08854, USA"},{"name":"Keck Center for Collaborative Neuroscience, Rutgers, The State University of New Jersey, 604 Allison Road, D251, Piscataway, NJ 08854, USA"},{"name":"Department of Genetics and the Human Genetics Institute of New Jersey, Rutgers, The State University of New Jersey, Piscataway, NJ 08854, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"G. Duygu","family":"Yilmaz","sequence":"additional","affiliation":[{"name":"Department of Cell Biology and Neuroscience, Rutgers, The State University of New Jersey, Piscataway, NJ 08854, USA"},{"name":"Keck Center for Collaborative Neuroscience, Rutgers, The State University of New Jersey, 604 Allison Road, D251, Piscataway, NJ 08854, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lauren A.","family":"Poppi","sequence":"additional","affiliation":[{"name":"Department of Genetics and the Human Genetics Institute of New Jersey, Rutgers, The State University of New Jersey, Piscataway, NJ 08854, USA"},{"name":"Child Health Institute of New Jersey, Robert Wood Johnson Medical School, New Brunswick, NJ 08901, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3936-6734","authenticated-orcid":false,"given":"Tess F.","family":"Kowalski","sequence":"additional","affiliation":[{"name":"Department of Cell Biology and Neuroscience, Rutgers, The State University of New Jersey, Piscataway, NJ 08854, USA"},{"name":"Keck Center for Collaborative Neuroscience, Rutgers, The State University of New Jersey, 604 Allison Road, D251, Piscataway, NJ 08854, USA"},{"name":"Child Health Institute of New Jersey, Robert Wood Johnson Medical School, New Brunswick, NJ 08901, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"K. T.","family":"Ho-Nguyen","sequence":"additional","affiliation":[{"name":"Department of Cell Biology and Neuroscience, Rutgers, The State University of New Jersey, Piscataway, NJ 08854, USA"},{"name":"Child Health Institute of New Jersey, Robert Wood Johnson Medical School, New Brunswick, NJ 08901, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Junbing","family":"Wu","sequence":"additional","affiliation":[{"name":"Department of Cell Biology and Neuroscience, Rutgers, The State University of New Jersey, Piscataway, NJ 08854, USA"},{"name":"Child Health Institute of New Jersey, Robert Wood Johnson Medical School, New Brunswick, NJ 08901, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Matthew","family":"Matrongolo","sequence":"additional","affiliation":[{"name":"Department of Cell Biology and Neuroscience, Rutgers, The State University of New Jersey, Piscataway, NJ 08854, USA"},{"name":"Child Health Institute of New Jersey, Robert Wood Johnson 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USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nicolas L.","family":"Carayannopoulos","sequence":"additional","affiliation":[{"name":"Department of Cell Biology and Neuroscience, Rutgers, The State University of New Jersey, Piscataway, NJ 08854, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nithisha","family":"Cheedalla","sequence":"additional","affiliation":[{"name":"Department of Cell Biology and Neuroscience, Rutgers, The State University of New Jersey, Piscataway, NJ 08854, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Julianne","family":"McGinnis","sequence":"additional","affiliation":[{"name":"Department of Cell Biology and Neuroscience, Rutgers, The State University of New Jersey, Piscataway, NJ 08854, USA"},{"name":"Child Health Institute of New Jersey, Robert Wood Johnson Medical School, New Brunswick, NJ 08901, 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