Ctnnd2, also known as δ -catenin/NPRAP/Neurojungin, is an adhesive junction-associated protein in the delta subfamily of the β-catenin superfamily. It functions in Wnt signaling to regulate gene expression and modulate Rho GTPases of the Ras superfamily in cytoskeletal reorganization. Ctnnd2 is likely a key point where Wnt signaling meets Rho GTPases and is important for processes like synaptic function and neuronal development [1].

In mice, Ctnnd2-Knock out (KO) mice exhibit typical autism-like behaviors, such as reduced social interaction and more frequent stereotypic behaviors. They also have deficits in spatial learning and memory, with decreased actin polymerization and postsynaptic spine density in hippocampal CA1 neurons. ShRNA-induced knockdown of Rictor, a protein with reduced expression in Ctnnd2-KO mice, exacerbates spatial learning and memory deficits but not autism-like behaviors, suggesting Ctnnd2 is involved in spatial learning and memory via Rictor-mediated actin polymerization and synaptic plasticity [2]. Additionally, chronic sleep restriction in Ctnnd2 KO mice further impairs social ability, cognition, and increases repetitive behaviors, while also affecting dendritic spines and the PI3K/Akt-mTOR pathway [3].

In conclusion, Ctnnd2 plays essential roles in synaptic maturation, neuronal integrity, and spatial learning and memory. Mouse KO models have been crucial in revealing its role in autism-like behaviors and cognitive impairments, providing insights into the mechanisms underlying these neurodevelopmental disorders.

References:

1. Lu, Qun, Aguilar, Byron J, Li, Mingchuan, Jiang, Yongguang, Chen, Yan-Hua. 2016. Genetic alterations of δ-catenin/NPRAP/Neurojungin (CTNND2): functional implications in complex human diseases. In Human genetics, 135, 1107-16. doi:10.1007/s00439-016-1705-3. https://pubmed.ncbi.nlm.nih.gov/27380241/

2. Wang, Xiaoya, Xu, Man, Xu, Qingbao, Deng, Jing, Wang, Shali. . Rictor is involved in Ctnnd2 deletion-induced impairment of spatial learning and memory but not autism-like behaviors. In Frontiers in bioscience (Landmark edition), 26, 335-346. doi:10.52586/4947. https://pubmed.ncbi.nlm.nih.gov/34455763/

3. Xu, Man, Wang, Xiaoya, Wang, Luyi, Tao, Yihao, Tan, Shujiang. 2023. Effects of chronic sleep restriction on the neuro-phenotypes of Ctnnd2 knockout mice. In Brain and behavior, 13, e3075. doi:10.1002/brb3.3075. https://pubmed.ncbi.nlm.nih.gov/37226399/