Jackson Laboratory

NSG™ Variants Portfolio

NSG™ mouse model variants are the most highly immunodeficient
mice and the models of choice for cancer xenograft modeling, stem
cell biology, humanized mice, and infectious disease research.

Comparison of NSG™ Mouse Model Variants

Name & Stock Number	NOD.Cg-Prkdc^scidIl2rg^tm1Wjl/SzJ (005557)	NOD.Cg-Prkdc^scidIl2rg^tm1WjlTg(CMV-IL3,CSF2,KITLG)1Eav/MloySzJ (013062)	NOD.Cg-Rag1^tm1MomIl2rg^tm1Wjl/SzJ (007799)
Branded or common name	NSG™(branded name), NOD scid gamma	NSGS, NOD scid gamma Il3- GM-SF (NSG-SGM3)	NRG, NOD Rag gamma
Mature B cells	Absent	Absent	Absent
Mature T cells	Absent	Absent	Absent
Dendritic cells	Defective	Defective	Defective
Macrophages	Defective	Defective	Defective
Natural killer cells	Absent	Absent	Absent
Complement	Absent	Absent	Absent
Leakiness	Negligible	Absent	Absent
Irradiation tolerance	Low	Low	High
Lymphoma incidence	Low	Low	Low
Benefits	Engrafts the widest range of solid and hematological cancers, including ALL and AML Most sensitive host for cancer stem cells when compared to NOD scid or nude mice Longer lifespan than NOD scid; supports long-term engraftment studies and capabilities; >89 weeks median	Increased CD4+ FoxP3+ regulatory T cell population after CD34+ humanization Enhances human myelopoiesis and terminal differentiation after CD34+ humanization Increased efficiency of engrafting human acute myeloid leukemia (AML)	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 Greater tolerance to genotoxic agents compared to NSG
Considerations	No thymic lymphomas, can be used for long & short-term experiments Sensitive to irradiation	Compromised human stem cell regeneration Suppression of human erythropoiesis Reduction of human B-lymphopoiesis	No thymic lymphomas, can be used for long & short-term experiments Requires higher dose of irradiation to obtain human HSC engraftment The serum half-life of human IgG is greatly reduced in NSG-B2m due to defective FcRn function
References	Ishikawa et al. 2005; Shultz et al. 2005	Nicolini et al. 2004; Wunderlich et al. 2010; Billerbeck et al. 2015	Pearson et al. 2008; Brehm et al. 2010; Maykel et al. 2014

(continued)

Name & Stock Number	NOD.Cg-Mcph1^{Tg(HLA-A2.1)1Enge}Prkdc^scidIl2rg^tm1Wjl/SzJ (009617) NOD.Cg-Prkdc^scid Il2rg^tm1Wjl Tg(HLA-A/H2-D/B2M)1Dvs/SzJ (014570)	NOD.Cg-Tg(HLA-DRA0101,HLA-DRB10101) 1Dmz Prkdc^scid Il2rg^tm1Wjl/GckRolyJ (012479) NOD.Cg-Prkdc^scid Il2rg^tm1Wjl H2-Ab1^tm1Doi Tg(HLA-DRB1)31Dmz/SzJ (017637)	NOD.Cg-B2m^tm1Unc Prkdc^scid Il2rg^tm1Wjl/SzJ (010636) NOD.Cg-Prkdc^scid H2-K1^tm1Bpe H2-D1^tm1Bpe Il2rg^tm1Wjl/SzJ(023848)
Branded or common name	HLA Class I-A2 Transgenics NSG-HLA-A2.1 (009617) NSG-HLA-A2/HHD (014570)	HLA Class II Transgenics DR1 (012479) DR4 (017637)	MHC Class I-null NSG™ NSG B2m (010636) NSG-(K^bD^b)^null(023848)
Mature B cells	Absent	Absent	Absent
Mature T cells	Absent	Absent	Absent
Dendritic cells	Defective	Defective	Defective
Macrophages	Defective	Defective	Defective
Natural killer cells	Absent	Absent	Absent
Complement	Absent	Absent	Absent
Leakiness	Negligible	Negligible	Negligible
Irradiation tolerance	Low	Low	Low
Lymphoma incidence	Low	Low	Low
Benefits	High engraftment of HLA-A2-restricted immune cells after CD34+ humanization Enable functional CD4+ T cell responses to viral infection after CD34+ humanization (014570)	Useful for transplantation studies in the absence of xeno-GVHD Develop allo-GVHD post-engraftmentof DR4-negative CD4+ T cells (017637)	Resistant to xeno-GVHD (010636) Attenuated xeno-GVHD development post-hPBMC transplantation (023848) High hCD45+ cell engraftment (023848) Useful for studying mechanisms for xeno-GVHD
Considerations	No thymic lymphomas - can be used for long-term experiments Sensitive to irradiation	Reduced CD45+ cell engraftment compared to NSG Higher proportion of mice with no CD45+ cell engraftment as compared to NSG (017637)	Reduced survival post hCD34+ cell transplantation compared to NSG mice (023848)
References	Shultz et al. 2010	Covassin et al. 2011	Covassin et al. 2013

(continued)

Name & Stock Number	NOD.Cg-Prkdc^scid H2-Ab1^em1Mvw H2-K1^tm1BpeH2-D1^tm1Bpe Il2rg^tm1Wjl/SzJ (025216)	NOD.Cg-Prkdc^scid Il2rg^tm1Wjl Tg(IL15)1Sz/SzJ (030890)	NOD.Cg.Kit^W-41JTyr⁺Prkdc^scidIl2rg^tm1Wjl/ThomJ (026622)
Branded or common name	Class 1/Class 2 Knockout MHC I/II KO	NSG-IL15 IL-15	NBSGW
Mature B cells	Absent	Absent	Absent
Mature T cells	Absent	Absent	Absent
Dendritic cells	Defective	Defective	Defective
Macrophages	Defective	Defective	Defective
Natural killer cells	Absent	Absent	Absent
Complement	Absent	Absent	Absent
Leakiness	Negligible	Negligible	Negligible
Irradiation tolerance	Low	Low	Low
Lymphoma incidence	Low	Low	Low
Benefits	Most resistant to xeno-GVHD of all NSG variants Extended human IgG half-life compared to B2m knockouts (10636)	Increased abundance and function of human NK cells following CD34-humanization	Human CD34 cells engraft effectively without preconditioning irradiation Longer lifespan than other immunodeficient Kit mutants Increased human erythroid cells (bone marrow)
Considerations	Resistance to xeno-GVHD associated with reduced CD45+ cell expansion in vivo Radiation sensitive	Sensitive to irradiation	Although irradiation is not required for stem cell engraftment, NBSGW mice likely share the same sensitivity to genotoxic agents as other NSG strains
References	Brehm et al. 2018	Brehm et al. 2018	McIntosh et al. 2015

(continued)

Name & Stock Number	NOD.Cg-Prkdc^scidIl2rg^tm1WjlTg(SERPINA1*E342K)#Slcw/SzJ (028842)	NOD.Cg-Tlr4^lps-del Prkdc^scidIl2rg^tm1Wjl/SzJ (033704)
Branded or common name	NSG-PiZ	NSG-Tlr4 KO
Mature B cells	Absent	Absent
Mature T cells	Absent	Absent
Dendritic cells	Defective	Defective
Macrophages	Defective	Defective
Natural killer cells	Absent	Absent
Complement	Absent	Absent
Leakiness	Negligible	Negligible
Irradiation tolerance	Low	Low
Lymphoma incidence	Low	Low
Benefits	Engrafts human and allogeneic mouse hepatocytes without rejection	Residual mouse innate immune system cannot respond to Tlr4 agonists After humanization, NSG-Tlr4 KO are ideal for studying human TLR4-specific responses against tumors
Considerations	Shares the same sensitivity to genotoxic agents as other NSG strains	Shares the same sensitivity to genotoxic agents as other NSG strains
References	Borel, et al. 2017	Aryee, et al. 2019