Overview

Also Known As:NSG-Hprt^null

NSG-Hprt^null mice are NOD.scid.Il2Rγc^null ("NSG") animals with the Hprt^null knockout allele. The NSG model is permissive for xenograft/human tumor growth, with Hprt-deficiency allowing human tumors to be transplanted into culture and any mouse cells removed (via HAT selection).

Donating Investigator

Michael Wiles, The Jackson Laboratory

Genetic overview

Genetic Background	Generation

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

Hprt^em1Mvw

Allele Type	Gene Symbol	Gene Name
Endonuclease-mediated (Null/Knockout)	Hprt	hypoxanthine guanine phosphoribosyl transferase

View Genetics

Research Applications

Research Tools
Internal/Organ Research
Immunology, Inflammation and Autoimmunity Research
Virology Research
Cancer Research
Cardiovascular Research
Hematological Research
Developmental Biology Research

View All Research Applications

Base Price

Starting at:

$2,854.50 Domestic price Cryo Recovery

View Price List

Details

Detailed Description

NSG-Hprt^null mice are NOD.scid.Il2Rγc^null ("NSG"; Stock No. 005557) animals also harboring the Hprt^em1Mvw allele (Hprt^null). The Hprt^null mutation has as a frame shift and premature termination, resulting in function knockout. Hprt-deficiency causes hypoxanthine-aminopterin-thymidine (HAT)-inducible cell death, but renders the cell resistant to 6-thioguanine (6-TG) cytotoxicity.

NSG-Hprt^null females homozygous for all three mutations, and males that are homozygous for scid and hemizygous for the X-linked mutations Hprt^null and Il2Rγc^null, may be collectively referred to as homozygous NSG-Hprt^null mice.

These NSG-Hprt^null mice may be expected to have a similar phenotype as the NSG-Hprt^b-m3 model (Stock No. 012480) that has the Hprt^b-m3 knockout rather than the Hprt^em1Mvw knockout. The expected phenotype of NSG-Hprt^null mice is described below.
Although viable and fertile, homozygous NSG-Hprt^null mice are immunodeficient: they have no mature T cells or B cells, lack functional natural killer (NK) cells, have reduced numbers of lymphocytes and myeloid dendritic cells, and are deficient in cytokine signaling. The Hprt-deficiency results in biochemically defective stromal cells.
Like homozygous NSG mice, homozygous NSG-Hprt^null mice are designed to allow engraftment of human tissues and primary cancers, such as hematopoietic cancers (e.g., leukemia), melanoma, ER+ breast cancer xenografts, purified human CD4⁺ T cells (fractionated from human peripheral blood mononuclear cells [PBMC]), and other tissues. When human cancers are implanted in Hprt-deficient NSG mice, the mouse fibroblast and stromal cells replace the human stromal cells. Following tumor explantation into culture, any Hprt-deficient mouse cells can be eliminated by HAT selection; resulting in isolation of human cancer cells. Conversely, Hprt-deficient mouse cells can be enriched by 6-TG selection. These mice may be used to generate patient-specific low passage cell lines from primary cancers for use in chemosensitivity profiling and other applications.

Similar to other immunodeficient strains, maintaining homozygous NSG-Hprt^null mice in high health status (specific pathogen-free) vivaria promotes overall colony health. If homozygous NSG-Hprt^null 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, and categorized, up-to-date references.

Development

NSG-Hprt^null mice are NOD.scid.Il2Rγc^null ("NSG") animals with the Hprt^em1Mvw knockout allele (Hprt^null). NSG-Hprt^null mice harbor several mutations, as described below.

NSG mice are non-obese diabetic animals (NOD/ShiLtJ) harboring the spontaneous severe combined immunodeficiency mutation (Prkdc^scid) on chromosome 16 and the Il2Rγc^null mutation at ~101 Mbp on the X chromosome (Il2rg^tm1Wjl created by Dr. Warren J. Leonard [NIH]). NSG mice are described and available from The Jackson Laboratory Repository as Stock No. 005557.

The Hprt^em1Mvw knockout allele (Hprt^null) was created by Dr. Michael V. Wiles (The Jackson Laboratory) using CRISPR/Cas9 genome engineering in NSG mouse zygotes (Stock No. 005557). The hypoxanthine guanine phosphoribosyl transferase locus (Hprt) on the X chromosome (~53 Mbp) was targeted with a specific single guide RNA (sgRNA) to create an 18 bp deletion, resulting in a frame shift and premature termination. The founder mouse was bred to NSG mice, and the offspring were bred together to produce homozygous mice.

In 2014, Dr. Wiles sent NSG-Hprt^null triple mutant mice to The Jackson Laboratory Repository as Stock No. 026222. The colony is maintained by breeding females homozygous for all three mutations with males that are homozygous for scid and hemizygous for the X-linked mutations Hprt^null and Il2Rγc^null.

Control Suggestions

Approximate Controls

Depending upon the experiment, the following may be appropriate control strain(s):
--NOD.scid.IL2RγcKO ("NSG"; Stock No. 005557)
--NOD.scid (Stock No. 001303)
--NOD/ShiLtJ inbred mice (Stock No. 001976)

Additional Information

Considerations for Choosing Controls

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

Hprt^em1Mvw

Allele Symbol: Hprt^em1Mvw

Allele Name	endonuclease-mediated mutation 1, Michael Wiles
Allele Type	Endonuclease-mediated (Null/Knockout)
Allele Synonym(s)	Hprt^null
Gene Symbol and Name	Hprt, hypoxanthine guanine phosphoribosyl transferase
Gene Synonym(s)
Strain of Origin	NOD.Cg-Prkdc^scid Il2rg^tm1Wjl/SzJ
Chromosome	X
Molecular Note	This allele was generated by injecting Cas9 RNA and a specific single guide RNA (sgRNA) to create an 18 bp deletion, resulting in a frame shift and premature termination.

Disease/Phenotype

Disease Terms

Research Areas By Phenotype

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

Genotype: Prkdc^scid related

Research Tools
- Cancer Research
  - B and T cell deficiency, xenograft/transplant host
- Toxicology Research
  - 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

Cancer Research
- Tumor Resistance
- Tumor Suppressor Genes
- Other
  - tumor metastasis
- Toxicology
  - B and T cell deficiency, xenograft/transplant host
  - xenograft/transplant host
- Growth Factors/Receptors/Cytokines
Research Tools
- Cancer Research
  - anti-tumor activity
  - myeloma and hybridoma production
  - Leukemia
  - genes regulating lymphoma development
  - tumor immunology
  - hybridoma production
  - B and T cell deficiency, xenograft/transplant host
  - T cell deficiency
  - production of B and T cells, antibodies, and hybridomas
  - xenograft/transplant host
  - B, T, and NK cell deficiency, xenograft/transplant host
  - production of T cells and hybridoma
  - B cell deficiency
  - production of B cells and antibodies
- Developmental Biology Research
  - transplantation marker for embryonic and adult tissue
- Reproductive Biology Research
  - transplantation marker for embryonic and adult tissue
- Genetics Research
  - Tissue/Cell Markers: cell marker for bone marrow transplantation
  - Tissue/Cell Markers: transplantation marker for embryonic and adult tissue
- Cell Biology Research
- Immunology, Inflammation and Autoimmunity Research
  - B and T cell deficiency
  - specific complement deficiency
  - Macrophage Deficiency
  - T cell deficiency
  - B, T, and NK cell deficiency
  - NK Cell Deficiency
  - background strain for histocompatibility congenics
  - genes regulating susceptibility to infectious disease and endotoxin
  - T cell deficiency, xenograft/transplant host
  - production of T cell lines and hybridomas
  - B cell deficiency
  - production of B cells and antibodies
  - production of B cells, antibodies T cell lines, and hybridomas
- Toxicology Research
  - xenograft/transplant host
  - B and T cell deficiency, xenograft transplant host
Immunology, Inflammation and Autoimmunity Research
- CD Antigens, Antigen Receptors, and Histocompatibility Markers
  - genes regulating susceptibility to infectious disease and endotoxin
- Immunodeficiency
  - multiple immune defects
  - specific complement deficiency
  - B and T cell deficiency
  - T cell deficiency
  - Macrophage defects
  - NK Cell Deficiency
  - NK Cell and Cd8 T Cell defects
  - defects in humoral immune responses
  - B cell defects
  - B cell deficiency
  - B, T, and NK cell deficiency
- Immunodeficiency Associated with Other Defects
- Autoimmunity
  - specific complement deficiency
  - B and T cell deficiency
  - B cell deficiency
- T Cell Receptor Signaling Defects
  - B and T cell deficiency, xenograft/transplant host
  - B and T cell deficiency
- Lymphoid Tissue Defects
  - B and T cell deficiency
  - hematopoietic development
- Graft vs. Host Disease
- Inflammation
  - B and T cell deficiency
- Growth Factors/Receptors/Cytokines
Internal/Organ Research
- Lymphoid Tissue Defects
  - T cell deficiency
  - B and T cell deficiency
- Thymus Defects
  - B and T cell deficient
Virology Research
- B and T Cell Deficiency
  - AIDS research tool
Cardiovascular Research
- Vascular Defects
  - defective macrophage function
Hematological Research
- Immunological Defects
  - B and T cell deficiency
- Hematopoietic Defects
Developmental Biology Research
- Lymphoid Tissue Defects
  - hematopoietic defects
- Internal/Organ Defects
  - hematopoietic defects
  - Lymphoid Tissue Defects

Genotype: Il2rg^tm1Wjl related

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

Mammalian Phenotype Terms by Genotype

References

Additional - Hprt^em1Mvw related

Additional - Il2rg^tm1Wjl related

Additional - Prkdc^scid related

Technical Support

CONTACT TECHNICAL SUPPORT

Genotyping Protocols
- Probe:Il2rg-PROBE
- End Point Analysis:Prkdc End Point
- Sanger sequencing:Hprtalternate1
- Genotyping resources and troubleshooting
Breeding Considerations

NSG-Hprt^null females homozygous for all three mutations, and males that are homozygous for scid (Prkdc^scid) and hemizygous for the X-linked mutations Hprt^em1Mvw (Hprt^null) and Il2Rγc^null (Il2rg^tm1Wjl) may be collectively referred to as homozygous NSG-Hprt^null mice.
When maintaining a live colony, homozygous NSG-Hprt^null females may be bred with homozygous NSG-Hprt^null males.

Homozygous NSG-Hprt^null mice are immunodeficient. As such, and similar to other immunodeficient strains, maintenance in high health status (specific pathogen-free) vivaria promotes overall colony health. If homozygous NSG-Hprt^null 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.
- Additional Breeding and Husbandry Support
Citation
When using the NOD.Cg-Prkdc^scid Hprt^em1Mvw Il2rg^tm1Wjl/MvwJ mouse strain in a publication, please cite the originating article(s) and include JAX stock #026222 in your Materials and Methods section.

Animal Health Reports

Facility Barrier Level Descriptions

Production of mice from cryopreserved embryos or sperm occurs in a maximum barrier room, G200

Pricing & Availability

Cryo Recovery

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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

Cryorecovery - Pricing

Service/Product	Description	Price
	Homozygous forPrkdc<scid> and Hprt<em1Mvw>, Homozygous females and Hemizygous males for Il2rg<tm1Wjl>,

Related Products and Services

Frozen Mouse Embryo	NOD.Cg-Prkdc<scid> Hprt<em1Mvw> Il2rg<tm1Wjl> Frozen Embryos	$2595.00
Frozen Mouse Embryo	NOD.Cg-Prkdc<scid> Hprt<em1Mvw> Il2rg<tm1Wjl> Frozen Embryos	$2595.00
Frozen Mouse Embryo	NOD.Cg-Prkdc<scid> Hprt<em1Mvw> Il2rg<tm1Wjl> Frozen Embryos	$3373.50
Frozen Mouse Embryo	NOD.Cg-Prkdc<scid> Hprt<em1Mvw> Il2rg<tm1Wjl> Frozen Embryos	$3373.50

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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.

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.

The use of this mouse model is subject to the terms and conditions of the Limited License from The Broad Institute.

The use of this mouse model is subject to the terms and conditions of the Limited Use Label License from Caribou Biosciences, Inc.

Licensing Information

Phone: 207-288-6470

Email: TechTran@jax.org

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Also Known As:NSG-Hprtnull

Donating Investigator

Genetic overview

Research Applications

Base Price

Detailed Description

Development

Control Suggestions

Approximate Controls

Additional Information

Prkdcscid

Allele Symbol: Prkdcscid

Il2rgtm1Wjl

Allele Symbol: Il2rgtm1Wjl

Hprtem1Mvw

Allele Symbol: Hprtem1Mvw

Disease Terms

Research Areas By Phenotype

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

Genotype: Prkdcscid related

Genotype: Il2rgtm1Wjl related

Mammalian Phenotype Terms by Genotype

References

Additional - Hprtem1Mvw related

Additional - Il2rgtm1Wjl related

Additional - Prkdcscid related

Genotyping Protocols

Breeding Considerations

Citation

Animal Health Reports

Production of mice from cryopreserved embryos or sperm occurs in a maximum barrier room, G200

Live Mouse

Cryorecovery - Pricing

Related Products and Services

Payment Terms and Conditions

The Jackson Laboratory's Genotype Promise

Terms Of Use

Additional Use Restrictions Apply

Licensing Information

JAX® Mice, Products & Services Conditions of Use

No Warranty

Credit for PRODUCTS or SERVICES

Animal Care and Use for SERVICES

No Liability

Also Known As:NSG-Hprt^null

Prkdc^scid

Allele Symbol: Prkdc^scid

Il2rg^tm1Wjl

Allele Symbol: Il2rg^tm1Wjl

Hprt^em1Mvw

Allele Symbol: Hprt^em1Mvw

Genotype: Prkdc^scid related

Genotype: Il2rg^tm1Wjl related

Additional - Hprt^em1Mvw related

Additional - Il2rg^tm1Wjl related

Additional - Prkdc^scid related