Unc5b, the Uncoordinated-5 homolog B, is a guidance receptor involved in multiple biological processes. It is associated with pathways like Wnt/β -catenin signaling and plays a crucial role in maintaining the integrity of barriers such as the blood-brain barrier (BBB) and blood-retina barrier (BRB) [1,3]. It also impacts neural differentiation, macrophage function in atherosclerosis, and endothelial cell senescence, and is related to cancer progression in diseases like osteosarcoma and glioblastoma [2,3,5-7]. Genetic models, especially KO/CKO mouse models, are valuable for studying its functions.

In adult mice, inducible endothelial-specific deletion of Unc5B leads to BBB leak, as the brain capillaries convert to a barrier-incompetent state with reduced Claudin-5 and increased PLVAP expression, indicating its importance in maintaining BBB integrity [1]. In macrophages of mice with advanced atherosclerosis, conditional deletion of Unc5b (∆Unc5bMØ) leads to a 40% decrease in atherosclerotic plaque burden, reduced plaque complexity, and macrophage content, suggesting its role in promoting atherosclerosis progression [2]. In osteosarcoma, knockdown of UNC5B in vitro reduces the cells' capacity for migration and invasion and the EMT process, highlighting its potential as an aggressive biomarker [4].

In summary, Unc5b is essential for maintaining barrier integrity, regulating macrophage function in atherosclerosis, and influencing cancer cell behavior in osteosarcoma. Mouse models with Unc5b deletion have been instrumental in revealing its functions in these specific disease-related biological processes, providing insights into potential therapeutic targets for CNS diseases, atherosclerosis, and osteosarcoma.

References:

1. Boyé, Kevin, Geraldo, Luiz Henrique, Furtado, Jessica, Ackerman, Susan L, Eichmann, Anne. 2022. Endothelial Unc5B controls blood-brain barrier integrity. In Nature communications, 13, 1169. doi:10.1038/s41467-022-28785-9. https://pubmed.ncbi.nlm.nih.gov/35246514/

2. Schlegel, Martin, Cyr, Yannick, Newman, Alexandra A C, Fisher, Edward A, Moore, Kathryn J. 2024. Targeting Unc5b in macrophages drives atherosclerosis regression and pro-resolving immune cell function. In Proceedings of the National Academy of Sciences of the United States of America, 121, e2412690121. doi:10.1073/pnas.2412690121. https://pubmed.ncbi.nlm.nih.gov/39436659/

3. Furtado, Jessica, Geraldo, Luiz Henrique, Leser, Felipe Saceanu, Eichmann, Anne, Boyé, Kevin. 2023. Netrin-1 binding to Unc5B regulates Blood-Retina Barrier integrity. In bioRxiv : the preprint server for biology, , . doi:10.1101/2023.01.21.525006. https://pubmed.ncbi.nlm.nih.gov/36711611/

4. Pan, Ruilin, Zhang, Yiming, Cheng, Yanmei, Feng, Shanshan, Zheng, Xiaofei. 2024. Identification of UNC5B as a novel aggressive biomarker for osteosarcoma based on basement membrane genes. In Gene, 930, 148871. doi:10.1016/j.gene.2024.148871. https://pubmed.ncbi.nlm.nih.gov/39154972/