B6-hLAG3 Mouse

The Lymphocyte Activation Gene 3 (LAG3), also known as CD223, is a gene encoding a transmembrane protein that acts as an immune checkpoint receptor. It is primarily expressed on activated T cells (CD4+, CD8+, and regulatory T cells), natural killer (NK) cells, and plasmacytoid dendritic cells (pDCs) ^[1]. LAG3 plays a crucial role in immune regulation and homeostasis by delivering inhibitory signals to immune cells, particularly upon binding to its primary ligand, MHC class II molecules, and other ligands like FGL1. This binding leads to reduced T cell activation, proliferation, cytokine production, and cytolytic activity, ultimately contributing to T cell exhaustion in chronic infections and cancer ^[2]. Conversely, in autoimmune diseases, dysregulation of LAG3 can lead to rapid, immune-mediated tissue damage ^[3]. Therefore, LAG3 is implicated in a range of associated diseases, including various cancers (e.g., melanoma, colorectal cancer, non-small cell lung carcinoma, Hodgkin lymphoma, multiple myeloma), chronic infections (e.g., HIV, hepatitis B virus, tuberculosis), and autoimmune disorders (e.g., rheumatoid arthritis, Hashimoto's thyroiditis). Due to its significant role in immune suppression, LAG3 is a major target for cancer immunotherapy, with many anti-LAG3 monoclonal antibodies currently under clinical investigation ^[4].

The B6-hLAG3 mouse is a humanized model constructed by replacing the endogenous extracellular domain (aa.24~442) of the mouse Lag3 gene with the human LAG3 extracellular domain (aa.23~450). The murine signal peptide (aa.1~23) and aa.443~521 are preserved. B6-hLAG3 mice can be used for research into the pathogenesis of various diseases, including malignant tumors, chronic infections, and autoimmune diseases, as well as for the screening, development, and safety evaluation of LAG3-targeted drugs.