Overview

Also Known As:NSG-Quad; NSG-Q
, NSG-SGM3 CSF1, NSG-Quad

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).

Donating Investigator

Dr. Leonard D. Shultz, The Jackson Laboratory

Genetic overview

Genetic Background	Generation
	F4 (2021-01-04 00:00:00)

Prkdc^scid

Allele Type	Gene Symbol	Gene Name
Spontaneous	Prkdc	protein kinase, DNA activated, catalytic polypeptide

Il2rg^tm1Wjl

Allele Type	Gene Symbol	Gene Name
Targeted (Null/Knockout)	Il2rg	interleukin 2 receptor, gamma chain

Tg(CMV-IL3,CSF2,KITLG)1Eav

Allele Type
Transgenic (Inserted expressed sequence, Humanized sequence)

Tg(CSF1)3Sz

Allele Type
Transgenic (Inserted expressed sequence, Humanized sequence)

View Genetics

Research Applications

Immunology, Inflammation and Autoimmunity Research
Research Tools
Internal/Organ Research
Virology Research
Cancer Research

View All Research Applications

Base Price

Starting at:

$270.48 Domestic price for male 4-week

275.60 Domestic price for breeder pair

View Price List

Details

Detailed Description

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 Prkdc^scid and Il2rg^tm1Wjl 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.

Development

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-Prkdc^scid/J eggs. Founder line 3 was established and mated to NOD.Cg-Prkdc^scid Il2rg^tm1Wjl/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-Prkdc^scid mice for at least 11 generations.

This strain was created by mating NOD.Cg-Prkdc^scid Il2rg^tm1Wjl Tg(CSF1)3Sz/J (Stock No. 028654) mice and NOD.Cg-Prkdc^scid Il2rg^tm1Wjl 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.

Expression Data

Expressed Gene	KITLG, KIT ligand, human
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.

Control Suggestions

Approximate Controls

Additional Information

Considerations for Choosing Controls

Selected References

Svoboda DS; Barrasa MI; Shu J; Rietjens R; Zhang S; Mitalipova M; Berube P; Fu D; Shultz LD; Bell GW; Jaenisch R. 2019. Human iPSC-derived microglia assume a primary microglia-like state after transplantation into the neonatal mouse brain. Proc Natl Acad Sci U S A 116(50):25293-25303PubMed: 31772018 MGI: J:286091

View All References

Genetics

Prkdc^scid

Allele Symbol: Prkdc^scid

Allele Name	severe combined immunodeficiency
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-Igh^b/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*).

Il2rg^tm1Wjl

Allele Symbol: Il2rg^tm1Wjl

Allele Name	targeted mutation 1, Warren J Leonard
Allele Type	Targeted (Null/Knockout)
Allele Synonym(s)	[KO]gammac; CD132^-; gammac^-; gc^-; Il2rg^tm1Wjll; IL2Rgamma^null
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

Tg(CMV-IL3,CSF2,KITLG)1Eav

Allele Symbol: Tg(CMV-IL3,CSF2,KITLG)1Eav

Allele Name	transgene insertion 1, CJ Eaves
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.

Tg(CSF1)3Sz

Allele Symbol: Tg(CSF1)3Sz

Allele Name	transgene insertion 3, Leonard Shultz
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-Prkdc^scid
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.

Disease/Phenotype

Disease Terms

Research Areas By Phenotype

This mouse can be used to support research in many areas including:

Genotype: Il2rg^tm1Wjl related

Immunology, Inflammation and Autoimmunity Research
- Growth Factors/Receptors/Cytokines
Cancer Research
- Growth Factors/Receptors/Cytokines

Genotype: Prkdc^scid related

Research Tools
- Toxicology Research
  - xenograft/transplant host
- Cancer Research
  - B and T cell deficiency, xenograft/transplant host
Internal/Organ Research
- Lymphoid Tissue Defects
  - B and T cell deficiency
Immunology, Inflammation and Autoimmunity Research
- Immunodeficiency
  - B and T cell deficiency
Virology Research
- B and T Cell Deficiency
  - AIDS research tool

Immunology, Inflammation and Autoimmunity Research
- Growth Factors/Receptors/Cytokines
- T Cell Receptor Signaling Defects
  - B and T cell deficiency, xenograft/transplant host
- Immunodeficiency
  - B, T, and NK cell deficiency
Research Tools
- Immunology, Inflammation and Autoimmunity Research
  - B, T, and NK cell deficiency
- Toxicology Research
  - B and T cell deficiency, xenograft transplant host
- Neurobiology Research
- Cancer Research
  - B and T cell deficiency, xenograft/transplant host
Cancer Research
- Growth Factors/Receptors/Cytokines

Mammalian Phenotype Terms by Genotype

References

Svoboda DS; Barrasa MI; Shu J; Rietjens R; Zhang S; Mitalipova M; Berube P; Fu D; Shultz LD; Bell GW; Jaenisch R. 2019. Human iPSC-derived microglia assume a primary microglia-like state after transplantation into the neonatal mouse brain. Proc Natl Acad Sci U S A 116(50):25293-25303PubMed: 31772018 MGI: J:286091

Additional - Il2rg^tm1Wjl related

Additional - Prkdc^scid related

Additional - Tg(CMV-IL3,CSF2,KITLG)1Eav related

Additional - Tg(CSF1)3Sz related

Technical Support

CONTACT TECHNICAL SUPPORT

Genotyping Protocols
- Standard PCR:Tg(CSF1)3Sz
- Probe:Il2rg-PROBE
- End Point Analysis:Prkdc End Point
- QPCR:TG(CSF2)
- QPCR:TG(IL3)
- QPCR:TG(KITLG)
- Genotyping resources and troubleshooting
Dietary Information
- New Diet as of March 2015: Lab Diet® 5K0Q (6% fat)
Breeding Considerations

Females that are homozygous for the Prkdc^scid, Il2rg^tm1Wjl, and SGM3 alleles and hemizygous for the CSF1 transgene can be bred to males that are homozygous for the Prkdc^scid and SGM3 alleles and hemizygous for Il2rg^tm1Wjl (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.
- Additional Breeding and Husbandry Support
Mating System
- HOM HOM HOM HEMI X HOM HEMI HOM NCAR
  OR
  HOM HOM HOM NCAR X HOM HEMI HOM HEMI
Citation
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.

Animal Health Reports

Facility Barrier Level Descriptions

AX11 (Maximum)

Pricing & Availability

Available

Domestic
International

Domestic Pricing for

Commercial & For-Profit

Not-For-Profit & Academic

International Pricing for

Commercial & For-Profit

Not-For-Profit & Academic

Live Mouse

Age

Genotype

Price

weeks

Breeder Pair

Sex

Genotype

Price

Female
Male

Cryorecovery - Pricing

Service/Product	Description	Price
	Please inquire

Payment Terms and Conditions

Terms are granted by individual review and stated on the customer invoice(s) and account statement. These transactions are payable in U.S. currency within the granted terms. Payment for services, products, shipping containers, and shipping costs that are rendered are expected within the payment terms indicated on the invoice or stated by contract. Invoices and account balances in arrears of stated terms may result in The Jackson Laboratory pursuing collection activities including but not limited to outside agencies and court filings.

The Jackson Laboratory's Genotype Promise

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.

Terms Of Use

General Terms and Conditions

Questions about Terms of Use

Additional Use Restrictions Apply

Research institutions require an MTA, companies require a (no fee) commercial use agreement prior to shipping.

Licensing Information

Phone: 207-288-6470

Email: TechTran@jax.org

Also Known As:NSG-Quad; NSG-Q, NSG-SGM3 CSF1, NSG-Quad

Donating Investigator

Genetic overview

Research Applications

Base Price

Detailed Description

Development

Expression Data

Control Suggestions

Approximate Controls

Additional Information

Selected References

Prkdcscid

Allele Symbol: Prkdcscid

Il2rgtm1Wjl

Allele Symbol: Il2rgtm1Wjl

Tg(CMV-IL3,CSF2,KITLG)1Eav

Allele Symbol: Tg(CMV-IL3,CSF2,KITLG)1Eav

Tg(CSF1)3Sz

Allele Symbol: Tg(CSF1)3Sz

Disease Terms

Research Areas By Phenotype

This mouse can be used to support research in many areas including:

Genotype: Il2rgtm1Wjl related

Genotype: Prkdcscid related

Mammalian Phenotype Terms by Genotype

References

Additional - Il2rgtm1Wjl related

Additional - Prkdcscid related

Additional - Tg(CMV-IL3,CSF2,KITLG)1Eav related

Additional - Tg(CSF1)3Sz related

Genotyping Protocols

Dietary Information

Breeding Considerations

Mating System

Citation

Animal Health Reports

Live Mouse

Breeder Pair

Cryorecovery - Pricing

Payment Terms and Conditions

The Jackson Laboratory's Genotype Promise

Terms Of Use

Additional Use Restrictions Apply

Licensing Information

Also Known As:NSG-Quad; NSG-Q
, NSG-SGM3 CSF1, NSG-Quad

Prkdc^scid

Allele Symbol: Prkdc^scid

Il2rg^tm1Wjl

Allele Symbol: Il2rg^tm1Wjl

Genotype: Il2rg^tm1Wjl related

Genotype: Prkdc^scid related

Additional - Il2rg^tm1Wjl related

Additional - Prkdc^scid related