Immunodeficient Mouse and Xenograft Host Comparisons

From the most highly immunodeficient mouse available— NSG™ (005557) - to nude mice (002019), the JAX immunodeficient suite of mice are powerful xenograft models for studying solid and hematopoietic tumors, cancer stem cells, hematopoeisis, humanized mice and infectious disease.

Comparison table:

Name & Stock Number NOD.Cg-Prkdcscid
Il2rgtm1Wjl
/SzJ (005557)
NOD.Cg-Rag1tm1Mom
Il2rgtm1Wjl
/SzJ (007799) 
NOD.Cg-Prkdcscid
Il2rgtm1Wjl
Tg(CMV-IL3,CSF2,KITLG)1Eav/MloySzJ (013062) 
 NOD.CB17-Prkdcscid/J (001303)
Common name NSG™, NOD scid gamma NRG, NOD Rag gamma NSGS, NOD scid gamma Il3- GM-SF (NSG-SGM3) NOD scid
Mature B cells Absent Absent Absent Absent
Mature T cells Absent Absent Absent Absent
Dendritic cells Defective Defective Defective Defective
Macrophages Defective Defective Defective Defective
Natural killer cells  Absent Absent Absent Defective
Complement Absent Absent Absent Absent
Leakiness Very Low Absent Absent Low
Irradiation tolerance Low High Low Low
Lymphoma incidence Low Low Low High (thymic lymphoma)
Median survival > 89 weeks Not determined Not determined 36 weeks
Benefits
  • Supports engraftment of human peripheral blood & bone marrow 
  • Xenotransplantation of human tissues, cells & tumors
  • Long-term multilineage hematopoeitic stem cell repopulation similar to NSG mice
  • Engrafts human PBMC without irradiation similar to NSG
  • Engrafts a wide range of solid and hematological cancers
 
  • Increased CD4+ FoxP3+ regulatory T cell population
  • Enhances human myelopoiesis and terminal differentiation
  • Increased efficiency of engrafting human acute myeloid leukemia (AML)
  • Adoptive transfer recipient for study of autoimmune type 1 diabetes 
  • Engrafts hematopoietic cancer cell lines 
  • Xenotransplantation of some human tumors 
 
Considerations
  • No thymic lymphomas, can be used for long & short-term experiments 
  • Sensitive to irradiation 
  • No thymic lymphomas, can be used for long & short-term experiments 
  • Requires higher dose of irradiation to obtain human HSC engraftment
  • Compromised human stem cell regeneration
  • Suppression of human erythropoiesis
  • Reduction of human B-lymphopoiesis
  • Develops thymic lymphomas by 8-9 months, best used in short term experiments 
  • Sensitive to irradiation 
 
References

Ishikawa et al. 2005;
Shultz et al. 2005; Additional references

Pearson et al. 2008;
Brehm et al. 2010;
Maykel et al. 2014

Nicolini et al. 2004;
Wunderlich et al. 2010;
Billerbeck et al. 2015

Shultz et al. 1995

Comparison table (con't):

Name & Stock Number CBySmn.CB17-Prkdcscid/J (001803)
 
 B6.129S7-Rag1tm1Mom/J (002216)  J:NU (007850) NU/J (002019)
Common name BALB scid B6 Rag1 Nude Nude
Mature B cells Absent Absent Present Present
Mature T cells Absent Absent Absent Absent
Dendritic cells Present Present Present Present
Macrophages Present Present Present Present
Natural killer cells  Present Present Present Present
Complement Present Present Present Present
Leakiness Low Absent N/A N/A
Irradiation tolerance Low High High High
Lymphoma incidence High (thymic lymphoma) Low Low Low
Median survival Not determined Not determined Not determined Not determined
Benefits
  •  MHC haplotype (H2d) allows adoptive transfer from BALB/c donors 
  • Common BALB/cBy inbred background simplifies creation of compound immunodeficient mutants 
  • Therapeutic Ab testing 
  • Engrafts hematopoietic cancer cell lines, some primary cells 
 
  • MHC haplotype (H2b) allows adoptive transfer from B6 donors 
  • Common B6 inbred background simplifies creation of compound immunodeficient mutants 
  • Theapeutic Ab testing 
 
  • Engraftment of human & mouse tumor cell lines 
  • Well published/characterized 
  • Robust outbred stock
  • Hairless phenotype enhances assessment of tumor growth 
 

  • Engraftment of human & mouse tumor cell lines 
  • Well published/characterized 
  • Uniform genetics improve reproducibility 
  • Hairless phenotype enhances assessment of tumor growth 
 

Considerations
  • Innate immunity intact 
  • NK cell activity limits engraftment 
  • Sensitive to irradiation 
 
  • Innate immunity intact 
  • Poor host for primary cell transplantation 
 
  • Innate immunity intact 
  • Little engraftment of hematopoietic cancer cells 
  • Not suitable for primary cell transplantation 
 
  • Innate immunity intact 
  • Little engraftment of hematopoietic cancer cells 
  • Not suitable for primary cell transplantation 
 
References Nonoyama et al. 1993 Mombaerts et al. 1992 Kelland LR. 2004 Kelland LR. 2004

NOD.Cg-Prkdcscid Il2rgtm1Wjl/SzJ (005557) 

The most powerful immunodeficient model that has changed the face of oncology, stem cell and infectious disease research.

  • Commonly known as “NSG™” or “NOD scid gamma” (Shultz et al. 2005
  • Severe defects in innate and adaptive immunity 
  • Lacks mature T, B, and functional NK cells 
  • Deficient in signaling of multiple cytokines (IL2, IL4, IL7, IL9, IL15 and IL21), resulting in significantly improved engraftment of human tissues, hematopoietic stem cells, and peripheral blood mononuclear cells 
  • Resistant to lymphoma, allowing for long-term experiments 
  • Capable of maintaining a human tumor microenvironment after engraftment 
  • Low tolerance for irradiation

NOD.Cg-Rag1tm1MomIl2rgtm1Wjl/SzJ (007799)

  • Commonly known as "NRG" or "NOD Rag gamma” (Pearson et al. 2008
  • Severe defects in innate and adaptive immunity 
  • Lacks mature T, B, and functional NK cells
  • Engrafts human PBMC without irradiation
  • Tolerant to irradiation

NOD.Cg-PrkdscidIl2rgtm1WjlTg(CMV-IL3,CSF2,KITLG)1Eav/MloySzJ/ (013062)

  • Commonly known as "NSGS" or "NSG-SGM3"
  • The expression of several transgenic human cytokines supports higher levels of human myeloid cell expansion
  • Significant engraftment of patient-derived AML samples

NOD.CB17-Prkdcscid/J (001303)

  • Commonly called “NOD scid” (Shultz  et al. 1995
  • Lack functional T and B cells 
  • Thymus, lymph node, and spleen virtually devoid of lymphocytes 
  • NOD genetic background results in reduced NK cell activity, impaired complement pathway, and least “leakiness” of residual T and B cells of any scid strain
  • Accepts allogeneic and xenogeneic grafts very efficiently and has been used successfully to transplant a variety of normal and malignant human cells and tissues, including isolates from hematopoietic cancers 
  • Insulitis - and diabetes-free throughout life 
  • Often develops thymic lymphomas by eight and a half months 
  • Radiation-sensitive 
  • Part of our unique Genetic Stability Program 

CBySmn.CB17-Prkdcscid/J (001803)

 
  • Commonly called “BALB scid” 
  • Deficient in mature T and B cells (Nonoyama et al. 1993
  • Innate immunity remains intact 
  • Normal antigen presentation, myeloid development, and NK cell functions 
  • Most mice are devoid of immunoglobulins 
  • Older mice can become "leaky," producing small numbers of mature T and B cells 

B6.129S7-Rag1tm1Mom/J (002216)

  • Commonly called “B6 Rag1” 
  • Produces no mature T or B cells (Mombaerts et al. 1992
  • Innate immunity remains intact 
  • Defective in V(D)J recombination and has no CD3+ or T cell receptor alpha/beta positive cells 
  • Thymocytes are CD4- CD8- and most are IL2R+ 
  • Unlike scid mutants on the same genetic background, is considered “non-leaky” and is radiation-resistant 

J:NU (007850)

  • Commonly called “Outbred Nude” 
  • Segregating genetic background improves hybrid vigor 
  • Homozygous for the nude spontaneous mutation (Foxn1nu (Pantelouris EM. 1973; Flanagan SP. 1966)) 
  • Abnormal hair growth, making engraftment of human or mouse cancer cells, and tumor regression following treatment, easily observable 
  • Athymic: lack T cells and thus incapable of cell-mediated immunity, B cell development is partially defective 
  • Produces normal T cell precursors, and produces mature T cells with time 
  • Responses to thymus-dependent antigens (when detectable) are primarily IgM 

NU/J (002019)

  • Commonly called “Inbred Nude” 
  • Have a uniform genetic background that can improve experimental reproducibility 
  • Homozygous for the nude spontaneous mutation (Foxn1nu(Pantelouris EM. 1973; Flanagan SP. 1966))
  • Abnormal hair growth, making engraftment of human or mouse cancer cells, and tumor regression following treatment, easily observable 
  • Athymic:  lack T cells and thus incapable of cell-mediated immunity, B cell development is partially defective 
  • Produces normal T cell precursors, and produces mature T cells with time 
  • Responses to thymus-dependent antigens (when detectable) are primarily IgM 
  • Challenging breeder: begins to ovulate late (at two and a half months) and stops early (at about four months), but breeds better than Foxn1nu/nu mutants on other inbred genetic backgrounds