IMR Press / FBL / Volume 26 / Issue 8 / DOI: 10.52586/4947
Open Access Original Research
Rictor is involved in Ctnnd2 deletion-induced impairment of spatial learning and memory but not autism-like behaviors
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1 Cerebrovascular Disease Laboratory, Institute of Neuroscience, Chongqing Medical University, 400016 Chongqing, China
2 Department of Physiology, School of Basic Medical Sciences, Chongqing Medical University, 400016 Chongqing, China
3 Department of Neurosurgery, Nanchong Central Hospital, The Second Clinical Medical College, North Sichuan Medical College, 637100 Nanchong, Sichuan, China
4 Department of Operating room, Nanchong Central Hospital, The Second Clinical Medical College, North Sichuan Medical College, 637100 Nanchong, Sichuan, China
5 China National Clinical Research Center for Neurological Diseases, Beijing Tiantan Hospital, Capital Medical University, 100070 Beijing, China
*Correspondence: (Shali Wang)
Front. Biosci. (Landmark Ed) 2021, 26(8), 335–346;
Submitted: 2 July 2021 | Revised: 25 July 2021 | Accepted: 11 August 2021 | Published: 30 August 2021
Copyright: © 2021 The Author(s). Published by BRI.
This is an open access article under the CC BY 4.0 license (

Background: The CTNND2 gene which encodes a δ-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.


1. Ctnnd2/ 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-/- mice.

CTNND2 gene
mTOR signaling
Learning and memory
Fig. 1.
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