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

Ye W, Jiang Z, Li GX, Xiao Y, Lin S, Lai Y, Wang S, Li B, Jia B, Li Y, Huang ZL, Li J, Feng F, Li S, Yao H, Liu Z, Cao S, Xu L, Li Y, Wu D, Zeng L, Zhong M, Liu P, Wen ZS, Xu B, Yao Y, Pei D, Li P - J Hematol Oncol (2015)

Bottom Line: 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.

View Article: PubMed Central - PubMed

Affiliation: Key Laboratory of Regenerative Biology, South China Institute for Stem Cell Biology and Regenerative Medicine, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou, 510530, China. ye_wei@gibh.ac.cn.

ABSTRACT

Background: 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.

Methods: 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).

Results: 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.

Conclusions: The TEI score was effectively able to reflect the immunodeficiency of a mouse strain.

No MeSH data available.


Related in: MedlinePlus

Assessing the ability to withstand a leukemic xenograft in immunodeficient mice. Kaplan-Meyer survival analysis of NSI, IL2Rg−/−, NOD-scid, scid, Rag2−/−, nude, and WT mice injected with a high number (1 × 106, a), medium number (1 × 105, b), and low number (1 × 104, c) of K562-GFP cells. d The percentages of K562-GFP cells in the peripheral blood (PB) of each mouse in the same experiments in (a). Bars represent the mean percentages of human K562-GFP cells in the PB of mice from each strain (n = 5)
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Fig1: Assessing the ability to withstand a leukemic xenograft in immunodeficient mice. Kaplan-Meyer survival analysis of NSI, IL2Rg−/−, NOD-scid, scid, Rag2−/−, nude, and WT mice injected with a high number (1 × 106, a), medium number (1 × 105, b), and low number (1 × 104, c) of K562-GFP cells. d The percentages of K562-GFP cells in the peripheral blood (PB) of each mouse in the same experiments in (a). Bars represent the mean percentages of human K562-GFP cells in the PB of mice from each strain (n = 5)

Mentions: For an accurate quantification, we first evaluated the immunodeficiency of a mouse strain by measuring its ability to prevent hematologic tumor engraftment. We injected K562-GFP cells [26], a human chronic myeloid leukemia cell line with Philadelphia chromosome, which constitutively expressed green fluorescent protein (GFP) (Additional file 1: Figure S1) into the seven mouse strains without any preconditioning, and assessed the percentages of tumor cells in certain tissues of the recipients. Three groups of mice (five mice per group) were assayed with a high number (1 × 106, H), medium number (1 × 105, M), and low number (1 × 104, L) of grafts, respectively (Additional file 2: Figure S2). The survival curves of each group of the seven mouse strains are shown in Fig. 1. The median survival time was 19 days in NSI mice, 21 days in NOD-scid mice, 23 days in scid mice, and 45 days in IL2Rg−/− mice when 1 × 106 K562-GFP cells were injected (Fig. 1a). No K562 cells were detected in WT mice after transplantation (Fig. 1a). After the injection of 1 × 105 K562-GFP cells, successful reconstitution of leukemia was observed in NSI (medium survival time 27 days) and NOD-scid (medium survival time 48 days) mice (Fig. 1b), but not in IL2Rg−/−, scid, Rag2−/−, nude, or WT mice. The injection of 1 × 104 K562-GFP cells reconstituted leukemia in the NSI mice, whereas leukemia cells were under detectable in NOD-scid, IL2Rg−/−, scid, Rag2−/−, nude, or WT mice (Fig. 1c). Because K562 cells were not detected in the bone marrow (BM) or spleen (SP) of the seven strains tested, we then measured the percentages of K562 cells in the peripheral blood (PB) of each mouse and found that the engraftment efficiencies were highest in the NSI mice, followed by the NOD-scid, IL2Rg−/−, scid, Rag2−/−, and nude mice, in that order (Fig. 1d).Fig. 1


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

Ye W, Jiang Z, Li GX, Xiao Y, Lin S, Lai Y, Wang S, Li B, Jia B, Li Y, Huang ZL, Li J, Feng F, Li S, Yao H, Liu Z, Cao S, Xu L, Li Y, Wu D, Zeng L, Zhong M, Liu P, Wen ZS, Xu B, Yao Y, Pei D, Li P - J Hematol Oncol (2015)

Assessing the ability to withstand a leukemic xenograft in immunodeficient mice. Kaplan-Meyer survival analysis of NSI, IL2Rg−/−, NOD-scid, scid, Rag2−/−, nude, and WT mice injected with a high number (1 × 106, a), medium number (1 × 105, b), and low number (1 × 104, c) of K562-GFP cells. d The percentages of K562-GFP cells in the peripheral blood (PB) of each mouse in the same experiments in (a). Bars represent the mean percentages of human K562-GFP cells in the PB of mice from each strain (n = 5)
© Copyright Policy - open-access
Related In: Results  -  Collection

License 1 - License 2
Show All Figures
getmorefigures.php?uid=PMC4478639&req=5

Fig1: Assessing the ability to withstand a leukemic xenograft in immunodeficient mice. Kaplan-Meyer survival analysis of NSI, IL2Rg−/−, NOD-scid, scid, Rag2−/−, nude, and WT mice injected with a high number (1 × 106, a), medium number (1 × 105, b), and low number (1 × 104, c) of K562-GFP cells. d The percentages of K562-GFP cells in the peripheral blood (PB) of each mouse in the same experiments in (a). Bars represent the mean percentages of human K562-GFP cells in the PB of mice from each strain (n = 5)
Mentions: For an accurate quantification, we first evaluated the immunodeficiency of a mouse strain by measuring its ability to prevent hematologic tumor engraftment. We injected K562-GFP cells [26], a human chronic myeloid leukemia cell line with Philadelphia chromosome, which constitutively expressed green fluorescent protein (GFP) (Additional file 1: Figure S1) into the seven mouse strains without any preconditioning, and assessed the percentages of tumor cells in certain tissues of the recipients. Three groups of mice (five mice per group) were assayed with a high number (1 × 106, H), medium number (1 × 105, M), and low number (1 × 104, L) of grafts, respectively (Additional file 2: Figure S2). The survival curves of each group of the seven mouse strains are shown in Fig. 1. The median survival time was 19 days in NSI mice, 21 days in NOD-scid mice, 23 days in scid mice, and 45 days in IL2Rg−/− mice when 1 × 106 K562-GFP cells were injected (Fig. 1a). No K562 cells were detected in WT mice after transplantation (Fig. 1a). After the injection of 1 × 105 K562-GFP cells, successful reconstitution of leukemia was observed in NSI (medium survival time 27 days) and NOD-scid (medium survival time 48 days) mice (Fig. 1b), but not in IL2Rg−/−, scid, Rag2−/−, nude, or WT mice. The injection of 1 × 104 K562-GFP cells reconstituted leukemia in the NSI mice, whereas leukemia cells were under detectable in NOD-scid, IL2Rg−/−, scid, Rag2−/−, nude, or WT mice (Fig. 1c). Because K562 cells were not detected in the bone marrow (BM) or spleen (SP) of the seven strains tested, we then measured the percentages of K562 cells in the peripheral blood (PB) of each mouse and found that the engraftment efficiencies were highest in the NSI mice, followed by the NOD-scid, IL2Rg−/−, scid, Rag2−/−, and nude mice, in that order (Fig. 1d).Fig. 1

Bottom Line: 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.

View Article: PubMed Central - PubMed

Affiliation: Key Laboratory of Regenerative Biology, South China Institute for Stem Cell Biology and Regenerative Medicine, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou, 510530, China. ye_wei@gibh.ac.cn.

ABSTRACT

Background: 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.

Methods: 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).

Results: 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.

Conclusions: The TEI score was effectively able to reflect the immunodeficiency of a mouse strain.

No MeSH data available.


Related in: MedlinePlus