Quantitative evaluation of the immunodeficiency of a mouse strain by tumor engraftments

Wei Ye, Zhiwu Jiang, Guan-Xiong Li, Yiren Xiao, Simiao Lin, Yunxin Lai, Suna Wang, Baiheng Li, Bei Jia, Yin Li, Zhi-liang Huang, Jin Li, Fenglan Feng, Shuhua Li, Huihui Yao, Zixia Liu, Su Cao, Lin Xu, Yangqiu Li, Donghai Wu, Lingwen Zeng, Mei Zhong, Pentao Liu, Zhe-sheng Wen, Bing Xu, Yao Yao, Duanqing Pei, Peng Li

The mouse is an organism that is widely used as a mammalian model for studying human physiology or disease, and the development of immunodeficient mice has provided a valuable tool for basic and applied human disease research. Following the development of large-scale mouse knockout programs and genome-editing tools, it has become increasingly efficient to generate genetically modified mouse strains with immunodeficiency. However, due to the lack of a standardized system for evaluating the immuno-capacity that prevents tumor progression in mice, an objective choice of the appropriate immunodeficient mouse strains to be used for tumor engrafting experiments is difficult. In this study, we developed a tumor engraftment index (TEI) to quantify the immunodeficiency response to hematologic malignant cells and solid tumor cells of six immunodeficient mouse strains and C57BL/6 wild-type mouse (WT). Mice with a more severely impaired immune system attained a higher TEI score. We then validated that the NOD-scid-IL2Rg-/- (NSI) mice, which had the highest TEI score, were more suitable for xenograft and allograft experiments using multiple functional assays. The TEI score was effectively able to reflect the immunodeficiency of a mouse strain.