{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,17]],"date-time":"2026-05-17T07:09:24Z","timestamp":1779001764163,"version":"3.51.4"},"reference-count":43,"publisher":"IMR Press","issue":"8","license":[{"start":{"date-parts":[[2021,8,30]],"date-time":"2021-08-30T00:00:00Z","timestamp":1630281600000},"content-version":"unspecified","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Front. Biosci. (Landmark Ed)"],"abstract":"<jats:p>Background: The CTNND2 gene which encodes a \u03b4-catenin protein (CTNND2) is associated with multiple severe neurological disorders. However, the specific role of CTNND2 in spatial cognition and related mechanisms remains obscure. Methods: In this study, we generated a new line of Ctnnd2-Knock out (KO) mice with its exon2 deleted, and then characterized their behavioral phenotypes and explore the Biological mechanism. Results: Ctnnd2-KO mice were with typical autism-like behaviors as evidenced by reduced social interaction in three-chamber sociability test, more frequent stereotypic behaviors (self-grooming), and deficits in spatial learning and memory tested by the Morris water maze. Furthermore, the expression of Rictor protein, a core component of the mTORC2 complex, was significantly decreased in the hippocampus of mutant mice. ShRNA-induced knockdown of Rictor protein in the hippocampus of both Ctnnd2-KO mice and wild-type mice exacerbated spatial learning and memory deficits but did not affect their autism-like behaviors. Mechanistically, the hippocampal CA1 neurons of Ctnnd2-KO mice showed decreased actin polymerization, postsynaptic spine density. Down-regulation of Rictor resulted in altered expression of post-synaptic proteins such as GluR1 and ELKS, but not presynaptic protein Synapsin1, implying abnormal synaptic changes in KO mice. Conclusion: The CTNND2 gene is involved in spatial learning and memory via Rictor-mediated actin polymerization and synaptic plasticity. Our study provides a novel insight into the role and mechanisms of the Ctnnd2 gene in cognition at the molecular and synaptic levels. Highlights 1. Ctnnd2\u2212\/\u2212 mice exhibited autism-like behaviors and impaired spatial learning and memory. 2. Rictor was involved in the regulation of Ctnnd2-associated spatial cognition but not autism-like behaviors. 3. Rictor played a crucial role in spatial learning and memory by modulating postsynaptic changes in hippocampal neurons of Ctnnd2-\u2063\/- mice.<\/jats:p>","DOI":"10.52586\/4947","type":"journal-article","created":{"date-parts":[[2021,8,26]],"date-time":"2021-08-26T00:58:25Z","timestamp":1629939505000},"source":"Crossref","is-referenced-by-count":14,"title":["Rictor is involved in Ctnnd2 deletion-induced impairment of spatial learning and memory but not autism-like behaviors"],"prefix":"10.31083","volume":"26","author":[{"given":"Xiaoya","family":"Wang","sequence":"first","affiliation":[{"name":"Cerebrovascular Disease Laboratory, Institute of Neuroscience, Chongqing Medical University, 400016 Chongqing, China"},{"name":"Department of Physiology, School of Basic Medical Sciences, Chongqing Medical University, 400016 Chongqing, China"},{"name":"Department of Neurosurgery, Nanchong Central Hospital, The Second Clinical Medical College, North Sichuan Medical College, 637100 Nanchong, Sichuan, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Man","family":"Xu","sequence":"first","affiliation":[{"name":"Cerebrovascular Disease Laboratory, Institute of Neuroscience, Chongqing Medical University, 400016 Chongqing, China"},{"name":"Department of Physiology, School of Basic Medical Sciences, Chongqing Medical University, 400016 Chongqing, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Qingbao","family":"Xu","sequence":"first","affiliation":[{"name":"Department of Operating room, Nanchong Central Hospital, The Second Clinical Medical College, North Sichuan Medical College, 637100 Nanchong, Sichuan, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Feng","family":"Yang","sequence":"first","affiliation":[{"name":"China National Clinical Research Center for Neurological Diseases, Beijing Tiantan Hospital, Capital Medical University, 100070 Beijing, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hui","family":"Tang","sequence":"first","affiliation":[{"name":"Department of Neurosurgery, Nanchong Central Hospital, The Second Clinical Medical College, North Sichuan Medical College, 637100 Nanchong, Sichuan, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chuan","family":"Shao","sequence":"first","affiliation":[{"name":"Department of Neurosurgery, Nanchong Central Hospital, The Second Clinical Medical College, North Sichuan Medical College, 637100 Nanchong, Sichuan, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Luyi","family":"Wang","sequence":"first","affiliation":[{"name":"Cerebrovascular Disease Laboratory, Institute of Neuroscience, Chongqing Medical University, 400016 Chongqing, China"},{"name":"Department of Physiology, School of Basic Medical Sciences, Chongqing Medical University, 400016 Chongqing, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yan","family":"Wang","sequence":"first","affiliation":[{"name":"Cerebrovascular Disease Laboratory, Institute of Neuroscience, Chongqing Medical University, 400016 Chongqing, China"},{"name":"Department of Physiology, School of Basic Medical Sciences, Chongqing Medical University, 400016 Chongqing, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jing","family":"Deng","sequence":"first","affiliation":[{"name":"Cerebrovascular Disease Laboratory, Institute of Neuroscience, Chongqing Medical University, 400016 Chongqing, China"},{"name":"Department of Physiology, School of Basic Medical Sciences, Chongqing Medical University, 400016 Chongqing, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shali","family":"Wang","sequence":"first","affiliation":[{"name":"Cerebrovascular Disease Laboratory, Institute of Neuroscience, Chongqing Medical University, 400016 Chongqing, China"},{"name":"Department of Physiology, School of Basic Medical Sciences, Chongqing Medical University, 400016 Chongqing, China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"16242","published-online":{"date-parts":[[2021,8,30]]},"reference":[{"key":"ref1","doi-asserted-by":"crossref","unstructured":"Lu Q, Aguilar BJ, Li M, Jiang Y, Chen Y-H. 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