{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,28]],"date-time":"2026-07-28T21:34:32Z","timestamp":1785274472324,"version":"3.55.0"},"reference-count":59,"publisher":"American Association for the Advancement of Science (AAAS)","issue":"13","content-domain":{"domain":["www.science.org"],"crossmark-restriction":true},"short-container-title":["Sci. Adv."],"published-print":{"date-parts":[[2025,3,28]]},"abstract":"<jats:p>\n            Tourette\u2019s syndrome (TS) is a major neurodevelopmental disorder characterized by childhood-onset motor and vocal tics. A W88C mutation in\n            <jats:italic>WWC1<\/jats:italic>\n            gene is a notable risk factor for TS, but the underlying molecular mechanisms remain unclear due to the lack of suitable animal models. Here, we generate a mutant mouse line with human W88C mutation (W88C\n            <jats:sup>Mut<\/jats:sup>\n            mice), which exhibits behavioral deficits similar to those observed in patients with TS, including repetitive motor behaviors and sensorimotor gating abnormalities. The W88C mutation leads to the degradation of kidney and brain (KIBRA) protein via a proteasomal pathway, evokes dopamine release in the dorsal striatum, and disrupts synaptic function through the dysregulation of Hippo pathway. Neuron-specific overexpression of wild-type\n            <jats:italic>WWC1<\/jats:italic>\n            rescues synaptic and behavioral phenotypes in W88C\n            <jats:sup>Mut<\/jats:sup>\n            mice. Together, this study not only provides a valuable mouse model for studying TS but also offers fresh insights into the molecular and synaptic mechanisms underlying neurodevelopmental abnormalities in TS.\n          <\/jats:p>","DOI":"10.1126\/sciadv.adr4588","type":"journal-article","created":{"date-parts":[[2025,3,28]],"date-time":"2025-03-28T18:05:49Z","timestamp":1743185149000},"update-policy":"https:\/\/doi.org\/10.34133\/aaas_crossmark","source":"Crossref","is-referenced-by-count":9,"title":["<i>WWC1<\/i>\n            mutation drives dopamine dysregulation and synaptic imbalance in Tourette\u2019s syndrome"],"prefix":"10.1126","volume":"11","author":[{"ORCID":"https:\/\/orcid.org\/0009-0006-5799-1142","authenticated-orcid":true,"given":"Junkai","family":"Lv","sequence":"first","affiliation":[{"name":"Innovation Center for Brain Medical Sciences of the Ministry of Education, Huazhong University of Science and Technology, Wuhan 430030, China."},{"name":"Department of Pathophysiology, School of Basic Medicine and Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0007-7285-3722","authenticated-orcid":true,"given":"Shiqi","family":"Liang","sequence":"additional","affiliation":[{"name":"Innovation Center for Brain Medical Sciences of the Ministry of Education, Huazhong University of Science and Technology, Wuhan 430030, China."},{"name":"Department of Pathophysiology, School of Basic Medicine and Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0009-8999-485X","authenticated-orcid":true,"given":"Pengwei","family":"Qin","sequence":"additional","affiliation":[{"name":"Innovation Center for Brain Medical Sciences of the Ministry of Education, Huazhong University of Science and Technology, Wuhan 430030, 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Wuhan 430030, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8054-0725","authenticated-orcid":true,"given":"Wei","family":"Jing","sequence":"additional","affiliation":[{"name":"Innovation Center for Brain Medical Sciences of the Ministry of Education, Huazhong University of Science and Technology, Wuhan 430030, China."},{"name":"Department of Pathophysiology, School of Basic Medicine and Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China."},{"name":"Department of Anatomy, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2422-5656","authenticated-orcid":true,"given":"Youming","family":"Lu","sequence":"additional","affiliation":[{"name":"Innovation Center for Brain Medical Sciences of the Ministry of Education, Huazhong University of Science and Technology, Wuhan 430030, China."},{"name":"Department of Pathophysiology, School of Basic Medicine and Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China."},{"name":"Department of Physiology, School of Basic Medicine and Tongji Medical College, Huazhong University of Science and Technology, Wuhan 4030030, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5973-5795","authenticated-orcid":true,"given":"Tongmei","family":"Zhang","sequence":"additional","affiliation":[{"name":"Innovation Center for Brain Medical Sciences of the Ministry of Education, Huazhong University of Science and Technology, Wuhan 430030, China."},{"name":"Department of Pathophysiology, School of Basic Medicine and Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China."},{"name":"Department of Histology and embryology, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3559-8965","authenticated-orcid":true,"given":"Hao","family":"Li","sequence":"additional","affiliation":[{"name":"Innovation Center for Brain Medical Sciences of the Ministry of Education, Huazhong University of Science and Technology, Wuhan 430030, China."},{"name":"Department of Pathophysiology, School of Basic Medicine and Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, 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