NSG QUAD mice express the human cytokines CSF1 [colony stimulating factor 1 (macrophage)], interleukin-3 (IL3; IL-3), granulocyte/macrophage-stimulating factor(CSF2; GM-CSF), and Steel factor (KITLG; SCF or SF) on the immunodeficient NSG background. In humanized NSG QUAD mice, the human cytokines can be used to support the survival of human induced pluripotent stem cells (hiPSCs).
Dr. Leonard D. Shultz, The Jackson Laboratory
Genetic Background | Generation |
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F4
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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) |
Allele Type |
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Transgenic (Inserted expressed sequence, Humanized sequence) |
Starting at:
$270.48 Domestic price for male 4-week |
275.60 Domestic price for breeder pair |
NSG QUAD (NSG-Q) mice express human CSF1 [colony stimulating factor 1 (macrophage)] and the triple transgenic 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), and the human Steel factor gene (KITLG; SCF or SF) on the immunodeficient NSG (Stock No. 05557) background. NSG mice carry the Prkdcscid and Il2rgtm1Wjl alleles on the NOD/LtShiJ background; they should have no mature T cells or B cells, lack functional natural killer (NK) cells, have reduced numbers of lymphocytes and myeloid dendritic cells, and be deficient in cytokine signaling. These mice do not spontaneously develop diabetes. Mice that are homozygous for scid, hemizygous/homozygous for the X-linked Il2rg, homozygous for SGM3 and hemizygous for CSF1 are viable and fertile. Males homozygous for the CSF1 transgene do not produce viable sperm.
The CSF1 and SGM3 transgenes encode the human cytokines CSF1, IL3, GM-CSF (CSF2) and SCF, which function to support the stable engraftment of human myeloid lineages and regulatory T cell populations. SGM3 mice constitutively produce 2-4 ng/ml serum levels of human IL-3, GM-CSF, and SF. The NSG QUAD strain is an immunodeficient mouse model producing human cytokines that can be used to support the survival of human induced pluripotent stem cells (hiPSCs). Brains from NSG-QUAD mice transplanted with hiPSC-derived microglial precursors (iMPS) generate cells that develop microglial morphology and gene expression patterns similar to primary human microglia. In some brain areas, the donor cells represent up to 50% of the total number of microglia.
View our Resources for the NSG mouse model, including discussion forum, immunodeficient model comparison, and categorized, up-to-date references.
Similar to other immunodeficient strains, maintaining NSG-QUAD mice in high health status (specific pathogen-free) vivaria promotes overall colony health. If NSG-QUAD 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.
The CSF1 transgenic construct containing the human colony stimulating factor 1 (macrophage), CSF1, gene from the 157 Kb BAC clone RP11-19F3 was microinjected into the pronuclei of fertilized NOD.CB17-Prkdcscid/J eggs. Founder line 3 was established and mated to NOD.Cg-Prkdcscid Il2rgtm1Wjl/J (Stock No. 005557) mice.
For the SGM3 transgene, 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.
This strain was created by mating NOD.Cg-Prkdcscid Il2rgtm1Wjl Tg(CSF1)3Sz/J (Stock No. 028654) mice and NOD.Cg-Prkdcscid Il2rgtm1Wjl Tg(CMV-IL3,CSF2,KITLG)1Eav/J (Stock No. 013062) mice. Progeny were interbred until all offspring were homozygous for scid, hemizygous/homozygous for the X-linked Il2rg targeted mutation and homozygous for the SGM3 and hemizygous for the CSF1 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 | |
Expressed Gene | CSF1, colony stimulating factor 1, human |
Site of Expression | CSF1 encodes a cytokine involved in the regulation of macrophages. |
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. |
Allele Name | transgene insertion 3, Leonard Shultz |
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Allele Type | Transgenic (Inserted expressed sequence, Humanized sequence) |
Allele Synonym(s) | |
Gene Symbol and Name | Tg(CSF1)3Sz, transgene insertion 3, Leonard Shultz |
Gene Synonym(s) | |
Promoter | CSF1, colony stimulating factor 1, human |
Expressed Gene | CSF1, colony stimulating factor 1, human |
Site of Expression | CSF1 encodes a cytokine involved in the regulation of macrophages. |
Strain of Origin | NOD.Cg-Prkdcscid |
Chromosome | UN |
Molecular Note | This transgene consists of a 157 kb human BAC clone, RP11-19F3, containing the entire genomic sequence of the human CSF1 gene including the endogenous promoter. CSF1 is the only gene in the plasmid. |
Females that are homozygous for the Prkdcscid, Il2rgtm1Wjl, and SGM3 alleles and hemizygous for the CSF1 transgene can be bred to males that are homozygous for the Prkdcscid and SGM3 alleles and hemizygous for Il2rgtm1Wjl (Il2rg is an X-linked gene) and CSF1 alleles. The CSF1 transgene is infertile in the homozygous state. SPF (specific pathogen-free) conditions are recommended. Please see our NSG housing and breeding information for additional details.
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When using the NSG-Quad; NSG-Q
mouse strain in a publication, please cite the originating article(s) and include JAX stock #028657 in your Materials and Methods section.
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The Jackson Laboratory has rigorous genetic quality control and mutant gene genotyping programs to ensure the genetic background of JAX® Mice strains as well as the genotypes of strains with identified molecular mutations. JAX® Mice strains are only made available to researchers after meeting our standards. However, the phenotype of each strain may not be fully characterized and/or captured in the strain data sheets. Therefore, we cannot guarantee a strain's phenotype will meet all expectations. To ensure that JAX® Mice will meet the needs of individual research projects or when requesting a strain that is new to your research, we suggest ordering and performing tests on a small number of mice to determine suitability for your particular project. We do not guarantee breeding performance and therefore suggest that investigators order more than one breeding pair to avoid delays in their research.
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