Odad2-KO Mouse

Odad2, also known as outer dynein arm docking complex subunit 2 or ARMC4 (armadillo repeat-containing protein 4), is involved in crucial biological functions. It is associated with the regulation of the NF-κB signaling pathway and is potentially related to ciliary function [1,3,4,5]. The NF-κB pathway is pivotal in inflammation and cancer, highlighting the importance of Odad2 in these processes. Genetic models can be valuable for further understanding its function.

High expression of ARMC4 (Odad2) downregulated the expression of NF-κB-dependent genes, reduced NF-κB activity, cellular proliferation, anchorage-independent growth, and migratory ability in vitro, and decreased xenograft tumor growth in vivo, indicating its role as a negative regulator of NF-κB and a potential tumor suppressor in colorectal cancer [1]. Also, genetic variants of Odad2 (rs7893462) are associated with increased susceptibility to hepatocarcinogenesis and can serve as an overall survival biomarker for hepatitis B virus-related hepatocellular carcinoma after hepatectomy [2]. Mutations in ARMC4 (Odad2) cause primary ciliary dyskinesia with reduced numbers of outer dynein arms, severely impaired ciliary beating, and randomization of left/right body asymmetry, showing its importance in ciliary function [5].

In conclusion, Odad2 plays essential roles in regulating the NF-κB pathway, which is relevant to cancer development, and in ciliary function, related to primary ciliary dyskinesia. Studies on Odad2, especially through model-based research, contribute to understanding the mechanisms of colorectal cancer and hepatocellular carcinoma, as well as primary ciliary dyskinesia.

References:

1. Martin, Matthew, Mundade, Rasika, Hartley, Antja-Voy, Liu, Yunlong, Lu, Tao. 2022. Using VBIM Technique to Discover ARMC4/ODAD2 as a Novel Negative Regulator of NF-κB and a New Tumor Suppressor in Colorectal Cancer. In International journal of molecular sciences, 23, . doi:10.3390/ijms23052732. https://pubmed.ncbi.nlm.nih.gov/35269880/

2. Zeng, Zhiming, Liao, Xiwen, Huang, Ketuan, Peng, Tao, Zhu, Guangzhi. 2023. Outer dynein arm docking complex subunit 2 polymorphism rs7893462 modulates hepatocellular carcinoma susceptibility and can serve as an overall survival biomarker for hepatitis B virus-related hepatocellular carcinoma after hepatectomy: a cohort study with a long-term follow-up. In World journal of surgical oncology, 21, 322. doi:10.1186/s12957-023-03205-4. https://pubmed.ncbi.nlm.nih.gov/37833735/

3. Alipourgivi, Faranak, Motolani, Aishat, Qiu, Alice Y, Chen, Shuibing, Lu, Tao. 2023. Genetic Alterations of NF-κB and Its Regulators: A Rich Platform to Advance Colorectal Cancer Diagnosis and Treatment. In International journal of molecular sciences, 25, . doi:10.3390/ijms25010154. https://pubmed.ncbi.nlm.nih.gov/38203325/

4. Hjeij, Rim, Aprea, Isabella, Poeta, Marco, Santamaria, Francesca, Omran, Heymut. 2023. Pathogenic variants in CLXN encoding the outer dynein arm docking-associated calcium-binding protein calaxin cause primary ciliary dyskinesia. In Genetics in medicine : official journal of the American College of Medical Genetics, 25, 100798. doi:10.1016/j.gim.2023.100798. https://pubmed.ncbi.nlm.nih.gov/36727596/

5. Hjeij, Rim, Lindstrand, Anna, Francis, Richard, Katsanis, Nicholas, Omran, Heymut. 2013. ARMC4 mutations cause primary ciliary dyskinesia with randomization of left/right body asymmetry. In American journal of human genetics, 93, 357-67. doi:10.1016/j.ajhg.2013.06.009. https://pubmed.ncbi.nlm.nih.gov/23849778/