Selp-KO Mouse

SELP, which encodes P-selectin, is a cell adhesion molecule gene. P-selectin is expressed on activated endothelial cells and platelets and mediates rolling adhesion of leukocytes during inflammation [4]. It is involved in multiple biological processes such as inflammation, immune response, and thrombosis, and its expression and binding with its ligand PSGL-1 contribute to various pathophysiological mechanisms [3].

In a study on COVID-19, the homozygosity of SELP rs6127 (c.1807G > A; p.Asp603Asn) was associated with severe thrombosis in male patients, especially those over 50, as the gene is downregulated by testosterone [1]. In cervical cancer, elevated SELP expression in tumor endothelial cells was correlated with improved survival in radiotherapy-treated patients, with SELP + TECs interacting with CD8 + T cells via the ACKR1-CCL5 axis to enhance radiotherapy efficacy [2]. In sickle cell disease, P-selectin plays a role in the pathogenesis, and its inhibition has shown efficacy in mitigating vaso-occlusive events [3].

In summary, SELP is crucial in processes like inflammation, thrombosis, and anti-cancer immune response. Findings from human-based studies in COVID-19, cervical cancer, and sickle cell disease reveal its significance in disease-related biological processes, highlighting its potential as a therapeutic target.

References:

1. Fallerini, Chiara, Daga, Sergio, Benetti, Elisa, Renieri, Alessandra, Mari, Francesca. 2021. SELP Asp603Asn and severe thrombosis in COVID-19 males. In Journal of hematology & oncology, 14, 123. doi:10.1186/s13045-021-01136-9. https://pubmed.ncbi.nlm.nih.gov/34399825/

2. Huang, Qingyu, Yang, Wenhui, Wang, Fuhao, Hu, Qinyong, Liu, Chao. 2025. SELP+ TEC:CD8+ T cell crosstalk associates with improved radiotherapy efficacy in cervical cancer. In Molecular cancer, 24, 41. doi:10.1186/s12943-025-02244-7. https://pubmed.ncbi.nlm.nih.gov/39901166/

3. Gupta, Parul, Choudhari, Vaishali, Kumar, Ravindra. 2024. Exploring the genetic mechanisms: SELP gene's contribution to alleviating vaso-occlusive crisis in sickle cell disease. In Gene, 928, 148805. doi:10.1016/j.gene.2024.148805. https://pubmed.ncbi.nlm.nih.gov/39079562/

4. Zhang, Nan, Liu, Zhenghui, Yao, Longbiao, Mehta-D'souza, Padmaja, McEver, Rodger P. 2016. P-Selectin Expressed by a Human SELP Transgene Is Atherogenic in Apolipoprotein E-Deficient Mice. In Arteriosclerosis, thrombosis, and vascular biology, 36, 1114-21. doi:10.1161/ATVBAHA.116.307437. https://pubmed.ncbi.nlm.nih.gov/27102967/