Table 1.

Summary of the immunodeficient mouse strains developed over the last few decades described in this review.

Name of the strain (genetic description) (reference when first described)	Features of the mice
BRG or BALB/c-Rag2−/−Il2r γ−/− (C.Cg-Rag2tm1Fwa Il2rgtm1Sug/JicTac (Taconic) or C;129S4-Rag2tm1.1Flv Il2rgtm1.1Flv/J (Jackson)) (35)	-BALB/c background with Rag2 and Il2rg knockout; Taconic strain is completely congenic on BALB/c background whereas Jackson is on a 129 background -both models have higher radiation tolerance due to Rag2 mutation compared to Scid models -both models lack T, B, and NK cells and dysfunctional DCs
BRG-IL3/CSF2 (C;129S4-Rag2tm1.1Flv Csf2/Il3tm1.1(CSF2,IL3)Flv Il2rgtm1.1Flv/J) (36)	-similar to BRG -targeted replacement of mouse Il3 and Csf2 with coding regions with those of human -improve human myeloid cell reconstitution in the lung in particular alveolar macrophages
BRGS (C;129S4-Rag2tm1.1Flv IL2rgtm1.1F1vTg(SIRPA)1Flv (37)	-similar to BRG -heterozygous human SIRPA BAC transgene expression -allow better engraftment and maintenance of human hematopoietic cells compared to BRG mice to levels comparable to NSG mice
BRG-TPO or Rag2−/−Il2ry−/−-TPO (C;129S4-Rag2tm1.1Flv Thpotm1.1(TPO)Flv Il2rgtm1.1Flv)/J (38)	-similar to BRG -human TPO knock-in replacing mouse Tpo -support higher human myeloid-lymphoid and HSC engraftment compared to BRG -have reduced mouse platelets compared to BRG
Rag2−/−Il2ry−/−-SIRPAh/mIL6h/h or RGSKI-IL6 (39)	-similar to BRG -heterozygous human SIRPA BAC transgene expression and homozygous IL6 knock-in replacing mouse Il6 -CD47 expressed on human cells binds efficiently to the mouse BAC transgene-encoded human SIRPα enabling mouse phagocytes to tolerate and not engulf engrafted human cells -allow improved thymopoiesis and peripheral T cell reconstitution -allow higher frequencies of human memory and IgG producing B cells development with increased in total IgG and antigen-specific IgG levels
Rag2−/−Il2ry−/−-SIRPAh/mIL15h/m or SRG-15 (40)	-similar to BRG -heterozygous human SIRPA knock-in -homozygous knock-in IL15 replacing mouse Il15 -expression of human SIRPα enables mouse phagocytes to tolerate and not engulf engrafted human cells -support efficient development of human circulating and tissue-resident NK cells, intraepithelial lymphocytes and innate lymphoid cell subsets
MITRG (C;129S4-Rag2tm1.1Flv Csf1tm1(CSF1)Flv Csf2/Il3tm1.1(CSF2,IL3)Flv Thpotm1.1(TPO)Flv Il2rgtm1.1Flv/J) (41)	-similar to BRG -human CSF1, CSF2/IL3 and TPO knock-in replacing the respective mouse genes -enable the full recapitulation of human myeloid development and function due to the expression of human cytokines
MISTRG (C;A29S4-Rag2tm1.1Flv Csf1tm1(CSF1)FlvCsf2/Il3tm1.1(CSF2,IL3)Flv Thpotm1.1(TPO)Flv Il2rgtm1.1Flv Tg(SIRPA)1Flv/J) (41)	-similar to MITRG -human SIRPA BAC transgene expression -CD47 expressed on human cells binds efficiently to the mouse BAC transgene-encoded human SIRPα enabling mouse phagocytes to tolerate and not engulf engrafted human cells
MISTRG6 (42)	-similar to MISTRG -homozygous IL6 knock-in replacing mouse Il6 -allow the development of entire spectrum of human plasma cell neoplasia
Scid (Prkdcscid) (22)	-lack functional lymphocytes because of impaired VDJ rearrangement -have severe combined immunodeficiency affecting both B and T lymphocytes
NOD-Scid (NOD.Cg-Prkdcscid/J) (24)	-as Scid mice -NOD/ShiJic strain background contributes to defective mouse DCs and macrophages -have reduced complement and NK cells -harbour Sirpa polymorphism that allows interactions between mouse macrophages and human CD47
NOD-Scid -SGM3 (NOD.Cg-Prkdcscid Tg(CMV-IL3,CSF2,KITLG)1Eav (43)	-as NOD-Scid -transgenic expression of human IL-3, GM-CSF, and SCF under the CMV promoter -support higher level of human myeloid cell engraftment -induce exhaustion of human HSCs
NOG (NOD.Cg-PrkdcscidIl2rgtm1Sug/JicTac) (29)	-features similar to NOD-Scid -truncated intracytoplasmic domain of IL-2Rg leading to no signalling -have defective mouse NK cell development
NOG-EXL or NOG-IL3/CSF2 (NOD.Cg-PrkdcscidIl2rgtm1Sug(SV40/HTLV-IL3,CSF2)10-7Jic/JicTac) (44)	-similar to NOG -transgenic expression of human GM-CSF and IL-3 driven by the SRα promoter -support higher levels of human myeloid cell differentiation -support higher human DC and mast cells differentiation -allow more efficient human HSC engraftment
NOG-IL6 (NOD.Cg-PrkdcscidIl2rgtm1SugTg(CMV-IL6)1-1Jic/JicTac) (45)	-similar to NOG -transgenic expression of human IL-6 driven by the CMV promoter -allow enhanced human monocytes development
NOG-IL15 (NOD.Cg-PrkdcscidIl2rgtm1SugTg(CMV-IL2/IL15)1-1Jic/JicTac) (46)	-similar to NOG -transgenic expression of human IL-15 with a IL-2 signal peptide driven by the CMV promoter -allow extensive human NK cell proliferation and differentiation and human NK cells produce both granzyme A and perforin upon stimulation -allow engraftment and expansion of human NK cells following engraftment with CD56+ NK cells derived from human PBMCs
NRG or NOD-Rag1−/−Il2ry −/− (NOD.Cg-Rag1tm1MomIl2rgtm1Wjl/SzJ) (47)	-harbor Rag1null and IL2rγnull mutations -lack T, B, and NK cells and dysfunctional DCs and macrophages -have Sirpa polymorphism that allows interactions between mouse macrophages and human CD47
NRG-HLA-A2-DR4 or DRAG (NOD.Cg-Rag1tm1Mom Il2rgtm1Wjl Tg(HLA-DRA,HLA-DRB1*0401)39-2Kito/ScasJ) (48)	-similar to NRG -express chimeric human-mouse class II transgenes HLA-DRA/HLA-DRB1*0401 fused to the I-Ed MHC class II molecule -allow enhanced HLA-DR-matched HSC engraftment and subsequent human T cell and B cell development to study the development of autoimmune diseases -allow vaccine testing and generation of human IgM, IgG, IgA or IgE monoclonal antibodies
NSG (NOD.Cg-PrkdcscidIl2rgtm1Wjl/SzJ) (28)	-features similar to NOD-Scid -target mutation of Il2rg leading to no expression of IL-2 -have defective NK cell development
NSG-B2Mnull (NOD.Cg-B2mtm1Unc Prkdcscid Il2rgtm1Wjl/SzJ) (49)	-similar to NSG -are relatively resistant to GVHD
NSG-CSF1 (NOD.Cg-Prkdcscid Il2rgtm1Wjl Tg(CSF1)3Sz/SzJ) (50)	-similar to NSG -transgenic expression of human M-CSF -support higher human macrophage development
NSG-HLA-A2/HHD (NOD.Cg-Prkdcscid Il2rgtm1Wjl Tg(HLA-A/H2-D/B2M)1Dvs/SzJ) (51)	-similar to NSG -express human HLA class 1 heavy and light chains with B2M covalently linked to the MHC class 1, alpha1 and alpha2 binding domains of the human HLA-A2.1 gene, and the alpha3, cytoplasmic and transmembrane domains of the murine H2-Db -support T cell maturation and responses to human antigens presented by HLA-A2.1 molecule
NSG-HLA-A24/HHD (NOD.Cg-Prkdcscid Il2rgtm1Wjl Tg(HLA-A24/H2-D/B2M)3Dvs/Sz) (52)	-similar to NSG -express human HLA-A24.2 with B2M and murine H2-Db -support human T cell maturation and responses to human antigens presented by HLA-A24.2 molecule
NSG‐HLA‐A2/DR1 (NOD.Cg-Prkdcscid IL2rgtmlWjl/Sz Tg[HLA-DRA*0101,HLA-DRB1*0101]1Dmz/GckRolyJ Mcph1Tg(HLA-A2.1)1Enge/SzJ (48)	-similar to NSG -express human/mouse chimeric MHC Class II transgene (Tg(HLA-DRB1*01)1Dmz): parts of mouse MHC Class II H2-Ea and H2-Eb1 were replaced by the corresponding amino acids of the human MHC Class II protein -Tg(HLA-A2.1)1Enge integrated into chromosome 8 causing a duplication in Mcph1 resulting into functional knock-out of Mcph1 in homozygous mice -support human T cell maturation and responses to human antigens presented by the respective HLA molecules. -allow the engraftment of functional human Th1, Th2 and Th17 T cells
NSG- (KbDb)null(IAnull) (NOD.Cg-Prkdcscid H2-K1tm1Bpe H2-Ab1em1Mvw H2-D1tm1Bpe Il2rgtm1Wjl/SzJ) (49)	-similar to NSG -have MHC class I molecule (H2-K and D) and MHC class II deficiencies (IA) -are resistant to GVHD
NSG-IL6 NOD.Cg-PrkdcscidIl2rgtm1Wjl Tg(IL6)/Sz) (53)	-similar to NSG -transgenic expression of human IL-6 -allow higher levels of human CD3+ and Th17 T cell development -allow higher plasma levels of human IgM and IgG
NSG-SGM3 (NOD.Cg-PrkdcscidIl2rgtm1Wjl Tg(CMV-IL3,CSF2,KITLG)1Eav/MloySzJ) (54)	-similar to NSG -transgenic expression of human IL-3, GM-CSF and SCF under the CMV promoter -induce exhaustion of human HSCs -allow higher level of human myeloid cell and AML engraftment -allow rapid reconstitution of human T cells, with improved B cell differentiation and increased levels of NK cells
NSG-SGM3-CSF1 or QUAD (NOD.Cg-Prkdcscid Il2rgtm1Wjl Tg(CMV-IL3,CSF2,KITLG)1Eav Tg(CSF1)3Sz/J) (33)	- similar to NSG-SGM3 combined with features of NSG-CSF1
NSG KitW41/W41 or NSGW41 (NOD.Cg-KitW-41J Prkdcscid Il2rgtm1Wjl/WaskJ) (55)	-similar to NSG -loss of endogenous Kit function, conferred by the KitW-41J allele -have impaired endogenous mouse HSCs, allowing engraftment of human HSCs without irradiation -support better human erythropoiesis and platelet formation