S1pr1-KO Mouse

S1pr1, short for sphingosine-1-phosphate receptor 1, is a G-protein coupled receptor for sphingosine 1-phosphate (S1P). It belongs to the sphingosine-1-phosphate receptor subfamily and is involved in multiple biological processes. S1pr1 plays crucial roles in regulating endothelial cell cytoskeletal structure, cell migration, immunomodulation, vasculogenesis during embryogenesis, and T cell egress [3].

In the context of osteoimmunology, S1P-S1PR1 signaling is a key regulator. Deletion or inhibition of this signaling axis can affect both bone remodeling directly by targeting osteoclastogenesis and osteogenesis, and indirectly by modulating the function and polarization of inflammatory cells in both adaptive and innate immune systems. This indicates its potential role in maintaining normal bone turnover and its implication in bone-related diseases like rheumatoid arthritis, spondyloarthritis, and periodontitis [1]. In ovarian cancer, S1PR1 deletion inhibits cell proliferation and migration, promotes cell senescence, and sensitizes cells to cisplatin chemotherapy, suggesting its role in cancer cell regulation through the PDK1-LATS1/2-YAP pathway [2]. In lung adenocarcinoma, S1PR1 expression is downregulated, and overexpression inhibits the malignant functions of cancer cells through the p-STAT1/miR-30c-5p/FOXA1 pathway, being positively correlated with prognosis [4]. Also, Sphk1/S1P/S1PR1 pathway differentially modulates the alloreactivity of CD4+ and CD8+ T cells, and inhibition of Sphk1 or S1PR1 can attenuate acute GVHD while retaining the graft-versus-leukemia effect [5].

In conclusion, S1pr1 is essential in various biological processes and disease conditions. Model-based research, especially gene knockout studies, has revealed its significance in bone remodeling, cancer cell regulation, and immune responses. Understanding S1pr1 can provide insights into the mechanisms of diseases such as bone-related disorders, ovarian and lung cancers, and graft-versus-host disease, potentially offering new therapeutic targets.