Csmd2, or CUB and Sushi multiple domains 2, encodes a single-pass transmembrane protein. The protein has a large extracellular domain with CUB and Sushi domain repeats. It is likely involved in regulating the complement cascade reaction of the immune system, and is associated with pathways related to neuron development and function, as well as cancer-related processes [1,2]. Genetic models, such as knockout (KO) mouse models, can be valuable for studying its functions.

In mouse models, Csmd2 is expressed in excitatory and inhibitory neurons in the forebrain. It localizes to dendritic spines and the postsynaptic density, interacting with synaptic scaffolding proteins like PSD-95 through its PDZ-binding domain on the cytoplasmic tail. Knock-down of Csmd2 in hippocampal neuron cultures leads to reduced dendritic arbor complexity and dendritic spine density, indicating its role in the development and maintenance of dendrites and synapses, which may be related to its association with psychiatric disorders [1]. In cancer research, pan-cancer analysis shows Csmd2 is upregulated in most tumors, has moderate to high diagnostic efficiency, and high expression is linked to poor prognosis. Its down-regulation in bladder cancer cell lines restrains cell viability, migration, and invasion [2,3].

In conclusion, Csmd2 plays essential roles in neuron development and synaptic maintenance, as revealed by mouse model-based research. In the context of disease, its dysregulation is associated with psychiatric disorders and cancer, highlighting the significance of Csmd2 KO/CKO mouse models in understanding these disease mechanisms.

References:

1. Gutierrez, Mark A, Dwyer, Brett E, Franco, Santos J. 2019. Csmd2 Is a Synaptic Transmembrane Protein that Interacts with PSD-95 and Is Required for Neuronal Maturation. In eNeuro, 6, . doi:10.1523/ENEURO.0434-18.2019. https://pubmed.ncbi.nlm.nih.gov/31068362/

2. Zhang, Huiyun, Huang, Taobi, Ren, Xiangqing, Sun, Weiming, Wang, Yuping. 2022. Integrated pan-cancer analysis of CSMD2 as a potential prognostic, diagnostic, and immune biomarker. In Frontiers in genetics, 13, 918486. doi:10.3389/fgene.2022.918486. https://pubmed.ncbi.nlm.nih.gov/36061177/

3. Yao, Zhijun, Yang, Hailang, Liu, Xiaoqiang, Deng, Wen, Fu, Bin. 2023. Preliminary study on the role of the CSMD2 gene in bladder cancer. In Heliyon, 10, e22593. doi:10.1016/j.heliyon.2023.e22593. https://pubmed.ncbi.nlm.nih.gov/38163223/