B6-hIL7R Mouse

The IL7R gene encodes the interleukin-7 receptor α chain (IL-7Rα), also known as CD127, a member of the type I cytokine receptor family. Expressed on T, B, NK, monocytes, and dendritic cells, IL7R gene expression is tightly regulated by transcription factors during immune cell development, playing a critical role in early T and B cell development and homeostasis ^[1]. IL-7Rα forms a functional receptor complex with the common γ chain receptor (IL2RG), constituting the IL-7 receptor. This complex activates downstream signaling pathways, including JAK-STAT5 and PI3K-AKT, which upregulate Bcl-2 and cell cycle regulators, promoting lymphocyte survival, proliferation, and differentiation, essential for T and B cell maturation ^[1-2]. The IL-7/IL-7Rα axis is central to maintaining peripheral T cell homeostasis, regulating memory T cell generation, and promoting thymic T cell output. It also influences NK cell development and innate lymphoid cell (ILC) maturation. Notably, IL7R gene polymorphisms are associated with autoimmune diseases, such as multiple sclerosis and systemic lupus erythematosus ^[1-3]. Dysregulation of IL-7R signaling is pathogenic; deficiency is linked to severe combined immunodeficiency (SCID) ^[4], while overexpression or aberrant activation may promote tumor growth, metastasis, and alter the tumor microenvironment ^[5]. Consequently, targeting the IL-7R pathway holds therapeutic potential for immune and tumor-related diseases, positioning IL-7Rα as a potential target in autoimmune diseases, immunodeficiency, and cancer ^[3-5].

The B6-hIL7R mouse is a humanized model constructed using gene editing technology, where the mouse IL7R endogenous extracellular domain was replaced with the human IL7R extracellular domain. The murine IL7R signal peptide and cytoplasmic region was preserved. Homozygous B6-hIL7R mice are viable and fertile. This model can be used for studying the pathological mechanisms and therapeutic approaches of autoimmune diseases, immunodeficiency, and cancer, and for the development of IL7R-targeted drugs.