The triple transgenic NSG-SGM3 (NSGS) mice expressing human IL3, GM-CSF (CSF2) and SCF (KITLG) combine the features of the highly immunodeficient NOD scid gamma (NSG) mouse with cytokines that support the stable engraftment of myeloid lineages and regulatory T cell populations. As a result, these NSG-SGM3 mice allow superior engraftment of diverse hematopoietic lineages and primary AML samples than other models and are useful for immuno-oncology, immunology and infectious disease studies.
James C Mulloy, Cincinnati Children's Hospital Medical Center
Genetic Background | Generation |
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Allele Type | Gene Symbol | Gene Name |
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Spontaneous | Prkdc | protein kinase, DNA activated, catalytic polypeptide |
Allele Type | Gene Symbol | Gene Name |
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Targeted (Null/Knockout) | Il2rg | interleukin 2 receptor, gamma chain |
Allele Type |
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Transgenic (Inserted expressed sequence, Humanized sequence) |
The triple transgenic NSG-SGM3 (NSGS) mice are NOD.scid.Il2Rγcnull ("NSG") animals with the SGM3 coinjected transgenes, each with a human cytomegalovirus promoter/enhancer sequence driving expression of the human interleukin-3 gene (IL3; IL-3), the human granulocyte/macrophage-stimulating factor gene (CSF2; GM-CSF), or the human Steel factor gene (KITLG; SCF or SF).
NSG-SGM3 mice combine the features of the highly immunodeficient NSG mouse with cytokines (IL3, GM-CSF and SCF) that support the stable engraftment of myeloid lineages and regulatory T cell populations. NSG-SGM3 mice allow superior engraftment of diverse hematopoietic lineages and primary AML samples than other models and are useful for immuno-oncology, immunology and infectious disease studies.
These NSG-SGM3 mice constitutively produce 2-4 ng/ml serum levels of human IL-3, GM-CSF, and SF.
Similar to other immunodeficient strains, maintaining NSG-SGM3 mice in high health status (specific pathogen-free) vivaria promotes overall colony health. If homozygous NSG-SGM3 animals are maintained in low health barrier rooms, the use of medicated water (e.g., sulfatrim/trimethoprim-sulfa or enrofloxacin/Baytril) is suggested to increase overall colony health.
View our Resources for the NSG mouse model, including discussion forum, immunodeficient model comparison, flow cytometry data and categorized, up-to-date references.
Three separate transgenes were designed each carrying either the human interleukin-3 gene (IL3; IL-3), the human granulocyte/macrophage-stimulating factor gene (CSF2; GM-CSF), or the human Steel factor gene (KITLG; SCF or SF). Expression of each gene is driven by a human cytomegalovirus promoter/enhancer sequence, and is followed by a human growth hormone cassette and a polyadenylation (polyA) sequence. The transgenes were microinjected into fertilized C57BL/6xC3H/HeN oocytes. The resulting founders, carrying all three transgenes (3GS) were backcrossed to BALB/c-scid/scid mice for several generations and subsequently backcrossed to NOD.CB17-Prkdcscid mice for at least 11 generations. These mice were bred to NOD.Cg-Prkdcscid Il2rgtm1Wjl mice, and were then interbred until all offspring were homozygous for 3GS and the IL2rg targeted mutation. Upon arrival at The Jackson Laboratory, transgenic mice were bred to NOD.Cg-Prkdcscid Il2rgtm1Wjl/SzJ mice (Stock No. 005557) for one generation to establish the colony. Thereafter, females homozygous for Prkdcscid, homozygous for Il2rgtm1Wjl and homozygous for the 3GS transgenes were bred with males homozygous for Prkdcscid, hemizygous for the X-linked Il2rgtm1Wjl and homozygous for the 3GS transgenes.
Expressed Gene | KITLG, KIT ligand, human |
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Expressed Gene | CSF2, colony stimulating factor 2, human |
Expressed Gene | IL3, interleukin 3, human |
Site of Expression |
Allele Name | severe combined immunodeficiency |
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Allele Type | Spontaneous |
Allele Synonym(s) | SCID |
Gene Symbol and Name | Prkdc, protein kinase, DNA activated, catalytic polypeptide |
Gene Synonym(s) | |
Site of Expression | T and B lymphocytes. |
Strain of Origin | C.BKa-Ighb/Icr |
Chromosome | 16 |
Molecular Note | A T-to-A transversion point mutation at a position corresponding to codon 4046 (codon 4095 in transcript ENSMUST00000023352.8) created a premature stop codon (p.Y4046*). |
Allele Name | targeted mutation 1, Warren J Leonard |
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Allele Type | Targeted (Null/Knockout) |
Allele Synonym(s) | [KO]gammac; CD132-; gammac-; gc-; Il2rgtm1Wjll; IL2Rgammanull |
Gene Symbol and Name | Il2rg, interleukin 2 receptor, gamma chain |
Gene Synonym(s) | |
Site of Expression | Primarily lymphoid cells. |
Strain of Origin | 129S4/SvJae |
Chromosome | X |
Molecular Note | A neomycin resistance cassette replaced part of exon 3 and all of exons 4 - 8 of the gene, resulting in the loss of most of the extracellular domain and all of the transmembrane and cytoplasmic domains of the protein. |
Mutations Made By | Dr. Warren Leonard, NHLBI, NIH |
Allele Name | transgene insertion 1, CJ Eaves |
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Allele Type | Transgenic (Inserted expressed sequence, Humanized sequence) |
Allele Synonym(s) | 3/GM/SF; SGM3; Tg(hSCF/hGM-CSF/hIL3 |
Gene Symbol and Name | Tg(CMV-IL3,CSF2,KITLG)1Eav, transgene insertion 1, CJ Eaves |
Gene Synonym(s) | |
Promoter | CMV, cytomegalovirus, human |
Expressed Gene | KITLG, KIT ligand, human |
Expressed Gene | CSF2, colony stimulating factor 2, human |
Expressed Gene | IL3, interleukin 3, human |
Strain of Origin | (C57BL/6 x C3H/HeN)F1 |
Chromosome | UN |
Molecular Note | cDNAs encoding human interleukin 3, colony stimulating factor 2 (granulocyte-macrophage) and kit ligand were independently ligated into expression cassettes in which the cDNA resides downstream of the cytomegalovirus (CMV) promoter/enhancer sequence and is followed by human growth factor intronic and polyadenylation sequences. A transgenic mouse that was shown by ELISA to have serum levels of all three growth factors at ng/ml levels was used to establish a line with the same phenotype. |
When maintaining a live colony, females homozygous for scid (Prkdcscid), homozygous for the X-linked Il2Rγcnull (Il2rgtm1Wjl) and homozygous for the SGM3 transgenes (Tg(CMV-IL3,CSF2,KITLG)1Eav) may be bred with males homozygous for scid, hemizygous for the X-linked Il2Rγcnull and homozygous for the SGM3 transgenes.
Homozygous NSG-SGM3 mice are immunodeficient. As such, and similar to other immunodeficient strains, maintaining NSG-SGM3 mice in high health status (specific pathogen-free) vivaria promotes overall colony health. If homozygous NSG-SGM3 animals are maintained in low health barrier rooms, the use of medicated water (e.g., sulfatrim/trimethoprim-sulfa or enrofloxacin/Baytril) is suggested to increase overall colony health. Also see additional NSG housing information.
When using the NSG-SGM3 mouse strain in a publication, please cite the originating article(s) and include JAX stock #013062 in your Materials and Methods section.
Facility Barrier Level Descriptions
RB16 (Maximum) |
EM01 (Maximum) |
RB08 (Maximum) |
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Sexes: Sexes of the same strain may be combined to reach minimum quantity levels to receive the volume pricing
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