Recombinant Mouse Fas/TNFRSF6/CD95 Fc Chimera Protein

Fas, also known as APO‑1 or CD95, belongs to the death receptor subfamily of the TNF receptor superfamily and is designated TNFRSF6 (1 ‑ 3). Mouse Fas cDNA encodes 327 amino acids (aa) that include a 21 aa signal peptide, a 148 aa extracellular domain (ECD) that contains three cysteine‑ich TNFR repeats, a 17 aa transmembrane sequence, and a 141 aa cytoplasmic domain containing a death domain (DD), which is required for transducing apoptotic signals (4). Mature mouse Fas ECD shares 68% aa sequence identity with rat Fas, and 53 ‑ 55% with human, feline, bovine and porcine Fas. One potentially secreted 63 aa isoform diverges at aa 61 (5). The Fas ligand (FasL, TNFSF6) is a type II transmembrane protein of the TNF family that can be expressed on activated T‑lymphocytes, NK cells and cells in immune privileged sites, or shed in soluble form (2). Polymorphisms of FasL impart differing activity of Fas depending on mouse strain (6). Engagement of FAS induces oligomerization of preformed Fas trimers (1, 2). The activated receptor recruits the adaptor molecule FADD to form the Death‑Inducing Signaling Complex (DISC). Upon activation, caspases in the DISC initiate the apoptotic signaling cascade (7). Fas is prominent in epithelial cells, hepatocytes, activated mature lymphocytes, virus‑transformed lymphocytes and tumor cells. It is an essential mediator in the activation‑induced death of T lymphocytes that terminates the immune reaction (1, 2, 8). In immune‑privileged tissues, infiltrating Fas‑bearing lymphocytes and inflammatory cells are killed by FasL engagement (9). Both humans and mice with genetic defects in Fas accumulate abnormal lymphocytes and develop systemic autoimmunity (1 ‑ 3). The Fas pathway also appears to cross‑communicate with the BIM (mitochondrial/intrinsic) apoptosis pathway (1).