B6-hOX40L (hTNFSF4) Mouse

The TNFSF4 gene (tumor necrosis factor superfamily member 4, also known as OX40L) encodes the OX40 ligand protein, a type II transmembrane protein mainly expressed on antigen-presenting cells (APCs, such as dendritic cells, B cells, and macrophages), as well as endothelial cells and smooth muscle cells ^[1]. This protein binds to the receptor OX40 (TNFRSF4) on the surface of T cells, providing crucial co-stimulatory signals that enhance T-cell proliferation, survival, and cytokine secretion, thereby playing a central role in adaptive immunity and inflammatory responses ^[2]. Dysregulated expression of TNFSF4 is associated with various autoimmune diseases, such as systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA), and its gene polymorphisms have been proven to be related to disease susceptibility ^[3]. Altering the OX40-OX40L interaction can either enhance the immune response to fight cancer or suppress it to treat autoimmune diseases ^[4]. Blocking the OX40-OX40L binding may alleviate autoimmune diseases by reducing the levels of pro-inflammatory cytokines and enhancing the function of regulatory T cells. Due to its crucial role in immune regulation, OX40L is regarded as an important target for treating autoimmune diseases and cancer immunotherapy, and current drug development focuses on monoclonal antibodies and OX40L inhibitors.

B6-hOX40L (hTNFSF4) mice are a humanized model constructed by using gene editing technology to replace the endogenous extracellular domain of the mouse Tnfsf4 gene with the extracellular domain of the human TNFSF4 gene. This model can be used for research on autoimmune diseases (such as systemic lupus erythematosus and rheumatoid arthritis), cancer immunology, and TNFSF4-targeted drug development.