A Novel Enhanced Green FluorescentProtein-Expressing NOG Mouse for Analyzingthe Microenvironment of Xenograft Tissues

The interaction between transplanted cells and host tissues is important for the growth and maintenance of transplanted cells. To analyze the mechanisms of these interactions, a systemic fluorescent protein-expressing mouse is a useful recipient. In this study, we generated a novel NOG strain, which strongly expresses enhanced green fluorescent protein (EGFP; PgkEGFP-NOG), especially in the liver, kidney, gastrointestinal tract, and testis. Because the host tissues expressed EGFP, xenotransplanted human cancer cells were clearly identified as EGFP-negative colonies in PgkEGFP-NOG mice. Immunohistochemical analysis revealed that EGFP-expressing stromal tissues formed a complicated tumor microenvironment within xenograft tissues. Moreover, a similar microenvironment was observed in human iPS cell-derived teratomas. Collectively, these results indicated that a suitable microenvironment is essential for the growth and maintenance of xenotransplanted cells and that PgkEGFP-NOG mice represent a useful animal model for analyzing the mechanisms of microenvironment formation.