B6-huOX40 (huTNFRSF4) Mouse

The TNFRSF4 gene encodes the protein OX40 (also known as CD134 or Tumor Necrosis Factor Receptor Superfamily Member 4), a cell-surface receptor belonging to the TNF-receptor superfamily. Its gene expression is primarily found on activated T cells (both CD4+ helper and CD8+ T cells), and also on other immune and non-immune cells, becoming upregulated following T cell activation, distinguishing it from constitutively expressed co-stimulatory molecules. The encoded protein acts as a co-stimulatory molecule, functioning as a receptor for its ligand, TNFSF4 (OX40L or CD252), which is expressed on antigen-presenting cells (APCs) ^[1]. The primary function of the OX40/OX40L axis is to deliver a crucial co-stimulatory signal that promotes T cell proliferation, enhances their survival (by suppressing apoptosis via pathways like NF-κB activation), and supports their differentiation into long-term effector and memory T cells, thus playing a vital role in sustaining the adaptive immune response ^[2]. Dysregulation of this pathway is implicated in various associated diseases, including autoimmune disorders such as systemic lupus erythematosus (SLE), rheumatoid arthritis, and Graves' disease, as well as cancers (e.g., in tumor-infiltrating lymphocytes, and some leukemias and carcinomas), where it's a target for immunotherapy, and Immunodeficiency 16 (IMD16), a primary immunodeficiency caused by loss-of-function variants ^[3-4].

B6-huOX40 (huTNFRSF4) mouse is a humanized model generated using gene editing technology, in which the mouse Tnfrsf4 endogenous extracellular domain is replaced with the human TNFRSF4 extracellular domain. The murine signal peptide was preserved. This model can be used for studying the pathological mechanisms and therapeutic approaches of autoimmune disorders, such as systemic lupus erythematosus (SLE), rheumatoid arthritis, and Graves' disease, as well as cancers and Immunodeficiency 16 (IMD16). It can also be used for the development of TNFRSF4-targeted drugs.