Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2010 Oct;24(10):1785-8.
doi: 10.1038/leu.2010.158. Epub 2010 Aug 5.

AML xenograft efficiency is significantly improved in NOD/SCID-IL2RG mice constitutively expressing human SCF, GM-CSF and IL-3

M Wunderlich, F-S Chou, K A Link, B Mizukawa, R L Perry, M Carroll, J C Mulloy

AML xenograft efficiency is significantly improved in NOD/SCID-IL2RG mice constitutively expressing human SCF, GM-CSF and IL-3

M Wunderlich et al. Leukemia. 2010 Oct.
No abstract available

PubMed Disclaimer

Conflict of interest statement

Conflict of interest: The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Characterization of the NSGS mouse. (a) Breeding scheme. NOD/SCID mice previously modified by IL2RG knockout (NSG) or expression of human cytokines (NSS) were crossbred to yield NOD/SCID IL2RG knockout with cytokine expression (NSGS). (b) Enzyme-linked immunosorbent assay assays with NSGS and NSS serum showed a high degree of correlation between hIL-3 and hGM-CSF expression. Cytokine heterozygotes and homozygotes were easily distinguished by this analysis. IL2RG status was determined by tail clip gDNA PCR. (c) Average cytokine expression in PB serum from NSGS and NSS mice. hIL-3, hGM-CSF and hSCF levels are shown. n = 15–21 mice per group, error bars = +/−s.d. (d) PB complete blood counts were determined by a Hemavet 950. n = 8–17 per group, error bars indicate s.d. No consistent differences were observed between strains. Top panel shows average total counts of specific cell types. Middle panel shows measures of red blood cell characteristics. Lower left and right panels show platelet numbers and volume, respectively. All mouse experiments were conducted according to an IRB approved protocol.
Figure 2
Figure 2
The NSGS mouse shows improved xenograft efficiency. (a) One million MA9.3-NRas(G12D) leukemic cells were injected into the tail vein of non-irradiated mice. Survival is shown over time. NSGS mice succumbed to AML faster than all other strains, including NSS (log rank test, P<0.0004). NS mice were consistently the least efficient (log rank test, P=0.065 vs NSG). (b) Homing assay. 10 million MA9 leukemic cells were injected by tail vein into sublethally irradiated (280 Rad) recipients. Human CD45 + CD33 + cells in the femurs were quantified 24h later by flow cytometry. Results are normalized to those obtained with NS hosts. (c) Mice injected with human leukemic cells as in ‘A’ were subjected to BM aspiration (top panel) and tail bleeds (bottom) to assess the xenograft status (percentage of CD45 + CD33 + cells by flow cytometry) on day 30. NSGS mice had significantly higher grafts than all others by Student's t-test (P<0.05). (d) Long-term cord blood cultures expressing AML1-ETO or CBFb-MYH11 were transferred to the left femurs of sublethally irradiated hosts by intrafemoral injection. The contralateral femur was analyzed at 8 weeks by BM aspiration. At 16 weeks, both the injected femur and a non-injected tibia were analyzed for the presence of human CD45 +CD33+ cells by flow cytometry. (e) Patient AML samples were injected into tail veins of sublethally irradiated NSG or NSGS mice. Xenografts were determined by BM aspiration and flow cytometry at 12–16 weeks. Shown are five samples with engraftment in the NSGS mice. When all these data were subjected to Student's t-test, NSGS grafts were significantly higher than NSG grafts (P= 0.05). Three additional samples were unable to engraft either mouse strain. No sample that engrafted NSG mice failed to engraft NSGS mice. (f) Flow cytometry plots showing significant human CD45 + cells in the BM of NSGS mice. AML cells were also detected in the spleen and PB. (g) Lineage stains indicate a myelomonocytic phenotype and significant CD34 + CD133 + population in the BM of primary mice as well as secondary recipients 16 or more weeks after transplant. All error bars represent s.d. *P<0.05 by Student's t-test. Flow cytometry performed on a BD FacsCantoII with BD antibodies (except anti CD133, Miltenyi Biotech) and analyzed with FlowJo software (Tree Star).
See this image and copyright information in PMC

References

    1. Shultz LD, Ishikawa F, Greiner DL. Humanized mice in translational biomedical research. Nature Reviews. 2007;7:118–130. - PubMed
    1. Ito M, Hiramatsu H, Kobayashi K, Suzue K, Kawahata M, Hioki K, et al. NOD/SCID/gamma(c)(null) mouse: an excellent recipient mouse model for engraftment of human cells. Blood. 2002;100:3175–3182. - PubMed
    1. Shultz LD, Lyons BL, Burzenski LM, Gott B, Chen X, Chaleff S, et al. Human lymphoid and myeloid cell development in NOD/LtSz-scid IL2R gamma null mice engrafted with mobilized human hemopoietic stem cells. J Immunol. 2005;174:6477–6489. - PubMed
    1. Feuring-Buske M, Gerhard B, Cashman J, Humphries RK, Eaves CJ, Hogge DE. Improved engraftment of human acute myeloid leukemia progenitor cells in beta 2-microglobulin-deficient NOD/SCID mice and in NOD/SCID mice transgenic for human growth factors. Leukemia. 2003;17:760–763. - PubMed
    1. Nicolini FE, Cashman JD, Hogge DE, Humphries RK, Eaves CJ. NOD/SCID mice engineered to express human IL-3, GM-CSF and Steel factor constitutively mobilize engrafted human progenitors and compromise human stem cell regeneration. Leukemia. 2004;18:341–347. - PubMed

Publication types

MeSH terms

Substances