B6-hHAVCR2 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 B6-hHAVCR2 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. B6-hHAVCR2 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.