huHAVCR2 Mouse

The HAVCR2 gene, also known as TIM-3 (T-cell immunoglobulin and mucin-domain containing-3) and CD366, is located on human chromosome 5q33.3 and encodes a cell surface receptor protein involved in modulating innate and adaptive immune responses. While generally considered an inhibitory immune checkpoint, its function can be context-dependent ^[1]. HAVCR2 expression is broad, found on various immune cells including CD4+ Th1 and Th17 cells, CD8+ T cells, regulatory T cells, natural killer (NK) cells, monocytes, macrophages, and dendritic cells ^[2]. It plays a crucial role in regulating macrophage activation, inhibiting Th1-mediated auto- and alloimmune responses, and promoting immunological tolerance, often by interacting with ligands like galectin-9 (LGALS9) and phosphatidylserine (PtSer) to suppress T-cell responses and induce apoptosis or anergy ^[3]. Mutations in HAVCR2 are strongly associated with autoimmune and inflammatory diseases, most notably subcutaneous panniculitis-like T-cell lymphoma (SPTCL) and hemophagocytic lymphohistiocytosis (HLH), where germline mutations can lead to persistent immune activation and cytokine release ^[4].

The huHAVCR2 mouse is a humanized model, constructed by replacing the mouse Havcr2 endogenous signal peptide and extracellular domain with the human HAVCR2 signal peptide and extracellular domain. The murine transmembrane-cytoplasmic region is preserved. huHAVCR2 mice can be used for research into the pathogenesis of various inflammatory diseases and cancers. They are also useful for the screening, development, and safety evaluation of HAVCR2-targeted drugs.