huCD16A(FCGR3A) Mouse

The FCGR3A gene (commonly known as CD16A) encodes the FcγRIIIA protein, a transmembrane receptor that binds the Fc portion of IgG with high functional affinity (particularly to immune complexes). This gene is primarily expressed in immune cells, most notably on Natural Killer (NK) cells, where it serves as a critical trigger for antibody-dependent cellular cytotoxicity (ADCC), as well as on subsets of monocytes and macrophages ^[1]. By binding to the Fc region of antibodies that have coated a target cell (such as a pathogen or tumor cell), the CD16A protein initiates intracellular signaling cascades that lead to the release of cytotoxic granules and pro-inflammatory cytokines ^[2]. While humans utilize FCGR3A, the mouse Fcgr4 gene serves as its functional ortholog, encoding the FcγRIV receptor that is essential for mediating similar IgG2-dependent effector functions in murine models ^[3]. In clinical contexts, polymorphisms in FCGR3A (such as the V158F variant) are significant because they influence the binding affinity for therapeutic antibodies, impacting the efficacy of monoclonal antibody treatments in oncology and autoimmune disorders ^[4]. Furthermore, dysregulation or mutations in this gene are associated with increased susceptibility to recurrent viral infections and systemic lupus erythematosus (SLE).

The huCD16A(FCGR3A) mouse model was generated by replacing the sequences from upstream of exon 1 to downstream of exon 5 of mouse Fcgr4 gene with the sequences from upstream of exon 1 to downstream of exon 6 of the human FCGR3A gene. This model is suitable for the study of various autoimmune diseases, such as systemic lupus erythematosus (SLE), as well as for oncology research, and for the screening, development, and safety evaluation of CD16A-targeted drugs.