Overview

Also Known As:NRG, NOD-Rag1^null IL2rg^null, NOD rag gamma

These mice are most commonly called NRG and are extremely immunodeficient. The mice carry two mutations on the NOD/ShiLtJ genetic background; a targeted knockout mutation in recombination activating gene 1 (Rag1) and a complete null allele of the IL2 receptor common gamma chain (IL2rg^null). The Rag1^null mutation renders the mice B and T cell deficient and the IL2rg^null mutation prevents cytokine signaling through multiple receptors, leading to a deficiency in functional NK cells. The severe immunodeficiency allows the mice to be humanized by engraftment of human CD34+ hematopoietic stem cells (HSC) and patient derived xenografts (PDX) at high efficiency. The immunodeficient NRG mice are more resistant to irradiation and genotoxic drugs than mice with a scid mutation in the DNA repair enzyme Prkdc.

Donating Investigator

Dr. Leonard D. Shultz, The Jackson Laboratory

Genetic overview

Genetic Background	Generation
	Contact Technical Support (2018-07-27 00:00:00)

Rag1^tm1Mom

Allele Type	Gene Symbol	Gene Name
Targeted (Null/Knockout)	Rag1	recombination activating gene 1

Il2rg^tm1Wjl

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

View Genetics

Research Applications

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

View All Research Applications

Base Price

Starting at:

$256.33 Domestic price for male 3-week

View Price List

Details

Detailed Description

These NRG mice are NOD-congenic mice harboring the Rag1^null mutation (Rag1KO or Rag1^tm1Mom) on chromosome 2 and the IL2rγ^null mutation (IL2RγcKO or Il2rg^tm1Wjl) on the X chromosome. These NRG mutant mice are also called NOD-Rag1^null IL2rγ^null double mutant mice or NOD.Rag1KO.IL2RγcKO mice. Females homozygous for both mutations (and males homozygous for Rag1^null; hemizygous for the X-linked IL2rγ^null mutation) are viable and fertile. When compared to NOD-scid IL2rg^null mice
(NSG mice; Stock No. 005557), these NRG mice tolerate much higher levels of irradiation conditioning. Additionally, NRG mice support higher levels of both human cord blood stem cell engraftment following irradiation-conditioning (leading to multi-lineage hematopoietic cell populations and a complete repertoire of human immune cells, including human T cells) and human peripheral blood mononuclear cells engraftment in unconditioned adult mice with respect to NOD-Rag1^null (Stock No. 003729) or NOD-scid (Stock No. 001303) mice. These NRG mice may be useful for cell or tissue transplantation studies, particularly as a model for human lymphohematopoietic cell engraftment studies that require a radioresistant host.

View Flow Cytometry Characterization Data for Immunodeficient JAX Strains

Development

These NRG mice are NOD-congenic mice harboring the Rag1^null mutation (Rag1KO or Rag1^tm1Mom) on chromosome 2 and the IL2rγ^null mutation (IL2RγcKO or Il2rg^tm1Wjl) on the X chromosome. These NRG mutant mice (also called NOD-Rag1^null IL2rγ^null double mutant mice or NOD.Rag1KO.IL2RγcKO mice) were produced by breeding NOD-Rag1^null (Stock No. 003729) mice with NOD-scid IL2rg^null
(Stock No. 005557)
mice. Offspring were intercrossed and bred to be homozygous for the Rag1^null mutation, homozygous (for females; or hemizygous for males) for the X-linked IL2rγ^null mutation, and wild-type for the scid mutation. The donating investigator reports that the genetic background is equivalent to approximately N9 prior to arrival at The Jackson Laboratory Repository.

Control Suggestions

Additional Information

Considerations for Choosing Controls

Selected References

Pearson T; Shultz LD; Miller D; King M; Laning J; Fodor W; Cuthbert A; Burzenski L; Gott B; Lyons B; Foreman O; Rossini AA; Greiner DL. 2008. Non-obese diabetic-recombination activating gene-1 (NOD-Rag1 null) interleukin (IL)-2 receptor common gamma chain (IL2r gamma null) null mice: a radioresistant model for human lymphohaematopoietic engraftment. Clin Exp Immunol 154(2):270-84PubMed: 18785974 MGI: J:140388

View All References

Genetics

Rag1^tm1Mom

Allele Symbol: Rag1^tm1Mom

Allele Name	targeted mutation 1, Peter Mombaerts
Allele Type	Targeted (Null/Knockout)
Allele Synonym(s)	Rag1^tm1Mom; targeted mutation 1, Peter Mombaerts
Gene Symbol and Name	Rag1, recombination activating gene 1
Gene Synonym(s)	Rag-1; RAG-1; RNF74; Rag-1
Site of Expression	expression is seen in bone marrow derived cell lines.
Strain of Origin	129S7/SvEvBrd-Hprt⁺
Chromosome	2
Molecular Note	A 1356 bp genomic fragment of the Rag1 gene, encoding the nuclear localization signal and the zinc-finger motif, was replaced by a neomycin cassette. A mutant transcript expressed from this allele was detected by Northern blot in bone marrow derived cell lines from homozygous mice.
Mutations Made By	Peter Mombaerts, Max Planck Research Unit for Neurogenetics

Il2rg^tm1Wjl

Allele Symbol: Il2rg^tm1Wjl

Allele Name	targeted mutation 1, Warren J Leonard
Allele Type	Targeted (Null/Knockout)
Allele Synonym(s)	Il2rg^tm1Wjl; targeted mutation 1, Warren J Leonard
Gene Symbol and Name	Il2rg, interleukin 2 receptor, gamma chain
Gene Synonym(s)	common cytokine receptor gamma chain; CIDX; IMD4; gc; IL-2RG; P64; [g]c; SCIDX; SCIDX1; common gamma chain; gamma C receptor; gamma(c); CD132; Ab2-183; Cd132; gammaC
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

Disease/Phenotype

Disease Terms

Research Areas By Phenotype

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

Genotype: Rag1^tm1Mom related

Hematological Research
- Immunological Defects
  - B and T cell deficiency
Immunology, Inflammation and Autoimmunity Research
- Immunodeficiency
  - B and T cell deficiency
- T Cell Receptor Signaling Defects
  - B and T cell deficiency
- Inflammation
  - B and T cell deficiency
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
Cancer Research
- Toxicology
  - B and T cell deficiency, xenograft/transplant host

Genotype: Il2rg^tm1Wjl related

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

Research Tools
- Cancer Research
  - B, T, and NK cell deficiency, xenograft/transplant host
  - xenograft/transplant host
- Immunology, Inflammation and Autoimmunity Research
  - T cell deficiency, xenograft/transplant host
- Toxicology Research
  - B and T cell deficiency, xenograft transplant host
  - xenograft/transplant host
Cancer Research
- Toxicology
  - xenograft/transplant host
  - B and T cell deficiency, xenograft/transplant host
Immunology, Inflammation and Autoimmunity Research
- T Cell Receptor Signaling Defects
  - B and T cell deficiency, xenograft/transplant host

Mammalian Phenotype Terms by Genotype

The following phenotype relates to a compound genotype created using this strain

Genotype: Il2rg^tm1Wjl/Y Rag1^tm1Mom/Rag1^tm1Mom
NOD.Cg-Rag1 Il2rg/SzJ

endocrine/exocrine gland phenotype

abnormal thymus morphology
- no lymphoid cells are present

absent thymus cortex
- no defined cortical region is observed

absent thymus medulla
- no defined medullary region is observed

thymus cysts
- thymus contains large cysts

immune system phenotype

abnormal adaptive immunity
- mature T and B cell populations are absent
- there are diminished CD3+CD4+ and CD3+CD8+ T cells and Igk+ light chain+ B cells in the spleen

abnormal innate immunity
- cells functioning in innate immunity are severely decreased in number

abnormal response to transplant
- CD4:CD8 human T cell ratios that are close to normal physiological values and high levels of human B cells are observed in spleens of mice compared to NOD.129S7(B6)-Rag1^tm1Mom mice
- engraftment of human lymphohematopoietic cells in blood and thymus, and peripheral blood mononuclear cells (PMBC) engraftment are higher than in NOD.129S7(B6)-Rag1^tm1Mom mice
- irradiated mice engrafted with human hematopoietic stem cells (HSCs) show much greater engraftment of human hematopoietic cells at 12 weeks than control NOD.129S7(B6)-Rag1^tm1Mom homozygotes
- levels of human CD45+ cell and CD3+ T cell engraftment are higher in spleens than in NOD.129S7(B6)-Rag1^tm1Mom mice
- percentages of human CD45+ cells engrafted in bone marrow are higher than in NOD.129S7(B6)-Rag1^tm1Mom homozygotes

abnormal spleen B cell follicle morphology
- spleen contains no follicles (or germinal centers)

abnormal spleen morphology
- spleen contains mainly myeloid-like cells and few lymphoid cells

abnormal thymus morphology
- no lymphoid cells are present

absent NK T cells
- natural killer cell (NK; DX5+LGL+ cells) are absent

absent thymus cortex
- no defined cortical region is observed

absent thymus medulla
- no defined medullary region is observed

decreased macrophage cell number
- levels are Gr-1-ve Mac-1+ve macrophages are reduced

thymus cysts
- thymus contains large cysts

hematopoietic system phenotype

abnormal spleen B cell follicle morphology
- spleen contains no follicles (or germinal centers)

abnormal spleen morphology
- spleen contains mainly myeloid-like cells and few lymphoid cells

abnormal thymus morphology
- no lymphoid cells are present

absent NK T cells
- natural killer cell (NK; DX5+LGL+ cells) are absent

absent thymus cortex
- no defined cortical region is observed

absent thymus medulla
- no defined medullary region is observed

decreased macrophage cell number
- levels are Gr-1-ve Mac-1+ve macrophages are reduced

thymus cysts
- thymus contains large cysts

References

Pearson T; Shultz LD; Miller D; King M; Laning J; Fodor W; Cuthbert A; Burzenski L; Gott B; Lyons B; Foreman O; Rossini AA; Greiner DL. 2008. Non-obese diabetic-recombination activating gene-1 (NOD-Rag1 null) interleukin (IL)-2 receptor common gamma chain (IL2r gamma null) null mice: a radioresistant model for human lymphohaematopoietic engraftment. Clin Exp Immunol 154(2):270-84PubMed: 18785974 MGI: J:140388

Additional References

Mombaerts P; Iacomini J; Johnson RS; Herrup K; Tonegawa S; Papaioannou VE. 1992. RAG-1-deficient mice have no mature B and T lymphocytes. Cell 68(5):869-77PubMed: 1547488 MGI: J:1934
Maykel J; Liu JH; Li H; Shultz LD; Greiner DL; Houghton J. 2014. NOD-scidIl2rg (tm1Wjl) and NOD-Rag1 (null) Il2rg (tm1Wjl) : a model for stromal cell-tumor cell interaction for human colon cancer. Dig Dis Sci 59(6):1169-79PubMed: 24798995 MGI: J:227975
Cao X; Shores EW; Hu-Li J; Anver MR; Kelsall BL; Russell SM; Drago J; Noguchi M; Grinberg A; Bloom ET; Paul WE; Katz SI; Love PE; Leonard WJ. 1995. Defective lymphoid development in mice lacking expression of the common cytokine receptor gamma chain. Immunity 2(3):223-38PubMed: 7697543 MGI: J:24117

Additional - Il2rg^tm1Wjl related

Additional - Rag1^tm1Mom related

Technical Support

CONTACT TECHNICAL SUPPORT

Genotyping Protocols
- Standard PCR:Laragen
- Probe:Il2rg-PROBE
- Standard PCR:Il2rg
- Standard PCR:Rag1Alternate1
- Probe:Rag1 Probe
- Genotyping resources and troubleshooting
Dietary Information
- LabDiet® 5K52 formulation (6% fat)
Breeding Considerations

This strain is a good breeder.

When maintaining a live colony, females homozygous for both the Rag1^null and IL2rγ^null mutations may be bred with males homozygous for the Rag1^null mutation and hemizygous for the X-linked IL2rγ^null mutation. The donating investigator suggests that NOD.129S7(B6)-Rag1^tm1Mom/J (Stock No. 003729), NOD/ShiLtJ (Stock No. 001976), or NOD/ShiLtSz may be appropriate controls.
- Additional Breeding and Husbandry Support
Mating System
- See "Breeding Considerations"
Citation
When using the NRG mouse strain in a publication, please cite the originating article(s) and include JAX stock #007799 in your Materials and Methods section.

Animal Health Reports

Facility Barrier Level Descriptions

AX30 (Maximum)

Pricing & Availability

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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.

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Licensing Information

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Also Known As:NRG, NOD-Rag1null IL2rgnull, NOD rag gamma

Donating Investigator

Genetic overview

Research Applications

Base Price

Detailed Description

Development

Control Suggestions

Additional Information

Selected References

Rag1tm1Mom

Allele Symbol: Rag1tm1Mom

Il2rgtm1Wjl

Allele Symbol: Il2rgtm1Wjl

Disease Terms

Research Areas By Phenotype

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

Genotype: Rag1tm1Mom related

Genotype: Il2rgtm1Wjl related

Mammalian Phenotype Terms by Genotype

Genotype: Il2rgtm1Wjl/Y Rag1tm1Mom/Rag1tm1MomNOD.Cg-Rag1 Il2rg/SzJ

endocrine/exocrine gland phenotype

immune system phenotype

hematopoietic system phenotype

References

Additional References

Additional - Il2rgtm1Wjl related

Additional - Rag1tm1Mom related

Genotyping Protocols

Dietary Information

Breeding Considerations

Mating System

Citation

Animal Health Reports

Live Mouse

Cryorecovery - Pricing

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:NRG, NOD-Rag1^null IL2rg^null, NOD rag gamma

Rag1^tm1Mom

Allele Symbol: Rag1^tm1Mom

Il2rg^tm1Wjl

Allele Symbol: Il2rg^tm1Wjl

Genotype: Rag1^tm1Mom related

Genotype: Il2rg^tm1Wjl related

Genotype: Il2rg^tm1Wjl/Y Rag1^tm1Mom/Rag1^tm1Mom
NOD.Cg-Rag1 Il2rg/SzJ

Additional - Il2rg^tm1Wjl related

Additional - Rag1^tm1Mom related