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A hCXCR1 transgenic mouse model containing a conditional color‐switching system for imaging of hCXCL8/IL‐8 functions in vivo

To address the functions of human CXCL8 (hCXCL8)/IL‐8 through hCXCR1 in vivo, we have developed a humanized, transgenic mouse for hCXCR1. This mouse line is versatile and allows for a variety of functional analyses using bioimaging, including Cre/loxP‐mediated, tissue‐specific hCXCR1 expression in a spatiotemporal manner; a color‐switching mechanism, which uses spectrum‐complementary, genetically encoded green and red fluorescence markers to label the hCXCR1‐expressing cells [enhanced GFP (eGFP)] against the background [monomeric red fluorescent protein (mRFP)]; a bioluminescent marker, which is present in the hCXCR1‐expressing cells; and an exogenous cell surface marker (eGFP moiety) in the hCXCR1‐expressing cells, which facilitates identification, isolation, and targeting of these cells. The established, transgenic founder line RCLG3A (TG+) expresses only mRFP and does so ubiquitously. When the RCLG3A mice are crossed with the tamoxifen‐inducible, whole‐tissue Cre mice (ROSA26‐Cre/Esr+/−), administration of tamoxifen induces whole‐body hCXCR1 expression and color‐switching. When RCLG3A mice are crossed with thymocyte‐specific Cre mice (Lck‐Cre+/+), the hCXCR1 expression and color‐switching are restricted in a lineage‐specific manner. This mouse line can be used to understand the functions of hCXCL‐8 in vivo. In addition, our approach and vectors can be used to establish other tissue‐specific, transgenic mice in conjunction with multifunctional cell markers, which facilitate cell imaging, tracing, and manipulation in vivo.