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

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

doi:10.1186/s13045-015-0156-y

Abstract

BackgroundThe 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.MethodsIn 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).ResultsMice 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.ConclusionsThe TEI score was effectively able to reflect the immunodeficiency of a mouse strain.Electronic supplementary materialThe online version of this article (doi:10.1186/s13045-015-0156-y) contains supplementary material, which is available to authorized users.

Highlights

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
We developed a tumor engraftment index (TEI), using six representative immunodeficient mouse models, combining the hematopoietic and solid tumor model and the allograft and xenograft models, and created a statistical formula for a simple and accurate method to quantify the immunodeficiency of mouse strains
After the injection of 1 × 105 K562-green fluorescent protein (GFP) cells, successful reconstitution of leukemia was observed in NSI and NOD-scid mice (Fig. 1b), but not in IL2Rg−/−, scid, Rag2−/−, nude, or wild-type mouse (WT) mice

Summary

Introduction

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. 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. Research on human diseases has relied on experiments using immunodeficient mouse models [1]. The limitations that impeded human cell engraftment in scid and recombination-activating 2 deficient (Rag2−/−) mice included the remaining mouse T and B cells and. With immunodeficient patients, STAT-1−/− and RAG−/− mice showed a significantly increased incidence of observable cancers compared with their nonimmunodeficient counterparts [11, 12]. A greater severity of immune deficiency led to a greater degree of tumor growth in immunodeficient mice

Methods

Results

Conclusion