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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

Hematopoietic functional assays of NSI mice. a Summary of percentages of human CD45+ cells in the PB, BM, and SP of NSI (red plot) and NOD-scid (blue plot) mice 20 weeks after injection with 1 × 104 or 1 × 105 purified human CD34+. Bars represent the mean percentages of human CD45+ cells in the PB, BM, and SP of mice from each group (n = 4 or 5 per group). *P ≤ 0.05 for bar 1 versus bar 2, bar 3 versus bar 4, bar 5 versus bar 6, bar 7 versus bar 8, and bar 11 versus bar 12; **P ≤ 0.01 for bar 9 versus bar 10. b Representative FACS analysis of percentages of multiple hematopoietic lineages in NSI as described in (a). c Representative fluorescence-activated cell sorting (FACS) analysis of percentages of multiple hematopoietic lineages in NSI transplanted with human cord blood CD34+/liver/thymus. d The level of human IgG (left) and OVA-specific IgG (right) in serum of NSI mice transplanted with human cord blood CD34+/liver/thymus. Open bars represent NSI mice that received human cord blood CD34+/liver/thymus (n = 3). Data are represented as the mean ± standard error of the mean. **P ≤ 0.01 for bar 3 versus bar 4 and bar 7 versus bar 8. e Representative FACS analysis of percentages of human CD45+ cells in NSI (right) and Nod-scid (left) transplanted with a single primary B-ALL cell
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Fig5: Hematopoietic functional assays of NSI mice. a Summary of percentages of human CD45+ cells in the PB, BM, and SP of NSI (red plot) and NOD-scid (blue plot) mice 20 weeks after injection with 1 × 104 or 1 × 105 purified human CD34+. Bars represent the mean percentages of human CD45+ cells in the PB, BM, and SP of mice from each group (n = 4 or 5 per group). *P ≤ 0.05 for bar 1 versus bar 2, bar 3 versus bar 4, bar 5 versus bar 6, bar 7 versus bar 8, and bar 11 versus bar 12; **P ≤ 0.01 for bar 9 versus bar 10. b Representative FACS analysis of percentages of multiple hematopoietic lineages in NSI as described in (a). c Representative fluorescence-activated cell sorting (FACS) analysis of percentages of multiple hematopoietic lineages in NSI transplanted with human cord blood CD34+/liver/thymus. d The level of human IgG (left) and OVA-specific IgG (right) in serum of NSI mice transplanted with human cord blood CD34+/liver/thymus. Open bars represent NSI mice that received human cord blood CD34+/liver/thymus (n = 3). Data are represented as the mean ± standard error of the mean. **P ≤ 0.01 for bar 3 versus bar 4 and bar 7 versus bar 8. e Representative FACS analysis of percentages of human CD45+ cells in NSI (right) and Nod-scid (left) transplanted with a single primary B-ALL cell

Mentions: We then used three types of functional assay to validate whether NSI mice were more suitable for xenograft than NOD-scid mice, as suggested by the TEI results. First, we compared the human hematopoietic engraftment capacities of the NSI mice and NOD-scid mice by engrafting the sub-lethally irradiated mice with 1 × 104 and 1 × 105 of human umbilical cord blood CD34+ cells, respectively. Twelve weeks after the transplantations, the percentages of human CD45+ cells in the PB, SP, and BM of the NSI mice were significantly higher than those of the NOD-scid mice (Fig. 5a). Furthermore, the injected human CD34+ cells differentiated into multiple hematopoietic lineages, including B cells, T cells, and myeloid cells (Fig. 5b).Fig. 5


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)

Hematopoietic functional assays of NSI mice. a Summary of percentages of human CD45+ cells in the PB, BM, and SP of NSI (red plot) and NOD-scid (blue plot) mice 20 weeks after injection with 1 × 104 or 1 × 105 purified human CD34+. Bars represent the mean percentages of human CD45+ cells in the PB, BM, and SP of mice from each group (n = 4 or 5 per group). *P ≤ 0.05 for bar 1 versus bar 2, bar 3 versus bar 4, bar 5 versus bar 6, bar 7 versus bar 8, and bar 11 versus bar 12; **P ≤ 0.01 for bar 9 versus bar 10. b Representative FACS analysis of percentages of multiple hematopoietic lineages in NSI as described in (a). c Representative fluorescence-activated cell sorting (FACS) analysis of percentages of multiple hematopoietic lineages in NSI transplanted with human cord blood CD34+/liver/thymus. d The level of human IgG (left) and OVA-specific IgG (right) in serum of NSI mice transplanted with human cord blood CD34+/liver/thymus. Open bars represent NSI mice that received human cord blood CD34+/liver/thymus (n = 3). Data are represented as the mean ± standard error of the mean. **P ≤ 0.01 for bar 3 versus bar 4 and bar 7 versus bar 8. e Representative FACS analysis of percentages of human CD45+ cells in NSI (right) and Nod-scid (left) transplanted with a single primary B-ALL cell
© Copyright Policy - open-access
Related In: Results  -  Collection

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getmorefigures.php?uid=PMC4478639&req=5

Fig5: Hematopoietic functional assays of NSI mice. a Summary of percentages of human CD45+ cells in the PB, BM, and SP of NSI (red plot) and NOD-scid (blue plot) mice 20 weeks after injection with 1 × 104 or 1 × 105 purified human CD34+. Bars represent the mean percentages of human CD45+ cells in the PB, BM, and SP of mice from each group (n = 4 or 5 per group). *P ≤ 0.05 for bar 1 versus bar 2, bar 3 versus bar 4, bar 5 versus bar 6, bar 7 versus bar 8, and bar 11 versus bar 12; **P ≤ 0.01 for bar 9 versus bar 10. b Representative FACS analysis of percentages of multiple hematopoietic lineages in NSI as described in (a). c Representative fluorescence-activated cell sorting (FACS) analysis of percentages of multiple hematopoietic lineages in NSI transplanted with human cord blood CD34+/liver/thymus. d The level of human IgG (left) and OVA-specific IgG (right) in serum of NSI mice transplanted with human cord blood CD34+/liver/thymus. Open bars represent NSI mice that received human cord blood CD34+/liver/thymus (n = 3). Data are represented as the mean ± standard error of the mean. **P ≤ 0.01 for bar 3 versus bar 4 and bar 7 versus bar 8. e Representative FACS analysis of percentages of human CD45+ cells in NSI (right) and Nod-scid (left) transplanted with a single primary B-ALL cell
Mentions: We then used three types of functional assay to validate whether NSI mice were more suitable for xenograft than NOD-scid mice, as suggested by the TEI results. First, we compared the human hematopoietic engraftment capacities of the NSI mice and NOD-scid mice by engrafting the sub-lethally irradiated mice with 1 × 104 and 1 × 105 of human umbilical cord blood CD34+ cells, respectively. Twelve weeks after the transplantations, the percentages of human CD45+ cells in the PB, SP, and BM of the NSI mice were significantly higher than those of the NOD-scid mice (Fig. 5a). Furthermore, the injected human CD34+ cells differentiated into multiple hematopoietic lineages, including B cells, T cells, and myeloid cells (Fig. 5b).Fig. 5

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