Cdhr4, belonging to the cadherin-related (CDHR) family, is involved in the constitution of intercellular junction complexes of the ependyma [1]. The ependyma is a crucial part of the ventricular system, and genes related to its development and function play important roles in maintaining normal cerebrospinal fluid movement.

In a study on AQP4 -/- mice (KO), which develop sporadic obstructive congenital hydrocephalus due to stenosis of Silvio's aqueduct, Cdhr4 expression was reduced. This reduction was accompanied by disorganized ependyma, changes in intercellular complex union, unevenly orientated cilia, and variations in the planar cell polarity of the apical membrane, ultimately leading to a reduced cilia beat frequency [1]. Additionally, Cdhr4 has been associated with stress disorders in GWAS studies, and its expression is downregulated in lung adenocarcinoma [2,3]. In esophageal cancer, Cdhr4 is among the cellular senescence-related genes used to calculate a risk score that is associated with overall survival, and in clear cell renal cell carcinoma, it is part of a nine-gene prognostic risk score [4,5]. In a genomics study on Chinese cattle breeds, Cdhr4 was related to environmental adaptability [6].

In conclusion, Cdhr4 is essential for the normal development and function of the ependyma as shown in the KO mouse model. Its involvement in multiple diseases, such as stress disorders, lung adenocarcinoma, esophageal cancer, and clear cell renal cell carcinoma, indicates its significance in disease-related biological processes. The gene also seems to play a role in environmental adaptability in cattle. Research on Cdhr4, especially through gene-knockout models, helps to understand its biological functions and its potential as a biomarker or therapeutic target in various diseases.

References:

1. Mayo, Francisco, González-Vinceiro, Lourdes, Hiraldo-González, Laura, Ramírez-Lorca, Reposo, Echevarría, Miriam. 2024. Impact of aquaporin-4 and CD11c + microglia in the development of ependymal cells in the aqueduct: inferences to hydrocephalus. In Fluids and barriers of the CNS, 21, 53. doi:10.1186/s12987-024-00548-2. https://pubmed.ncbi.nlm.nih.gov/38956598/

2. Zorkina, Y A, Golubeva, E A, Gurina, O I, Reznik, A M, Morozova, A Y. . [Genetic variants associated with the development of stress disorders: A systematic review of GWAS]. In Zhurnal nevrologii i psikhiatrii imeni S.S. Korsakova, 125, 12-26. doi:10.17116/jnevro202512503112. https://pubmed.ncbi.nlm.nih.gov/40195096/

3. Wang, Hong, Zhang, Shuai, Yuan, Xi, Wei, Yong, Wu, Zhiqiang. 2024. mRNA expression profile and prognostic values of the CDHR family genes in lung adenocarcinoma. In International journal of biological macromolecules, 281, 136642. doi:10.1016/j.ijbiomac.2024.136642. https://pubmed.ncbi.nlm.nih.gov/39419138/

4. Zheng, Shiyao, Lin, Nan, Wu, Qing, He, Hongxin, Yang, Chunkang. 2023. Prognostic model construction and validation of esophageal cancer cellular senescence-related genes and correlation with immune infiltration. In Frontiers in surgery, 10, 1090700. doi:10.3389/fsurg.2023.1090700. https://pubmed.ncbi.nlm.nih.gov/36761024/

5. Al Sharie, Ahmed H, Al Masoud, Eyad B, Jadallah, Rand K, El-Elimat, Tamam, Alali, Feras Q. . Transcriptome analysis revealed a novel nine-gene prognostic risk score of clear cell renal cell carcinoma. In Medicine, 103, e39678. doi:10.1097/MD.0000000000039678. https://pubmed.ncbi.nlm.nih.gov/39331921/

6. Mei, Chugang, Gui, Linsheng, Hong, Jieyun, Zhang, Song, Zan, Linsen. 2021. Insights into adaption and growth evolution: a comparative genomics study on two distinct cattle breeds from Northern and Southern China. In Molecular therapy. Nucleic acids, 23, 959-967. doi:10.1016/j.omtn.2020.12.028. https://pubmed.ncbi.nlm.nih.gov/33614243/