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 (IL2rgnull). The Rag1null mutation renders the mice B and T cell deficient and the IL2rgnull 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.
Dr. Leonard D. Shultz, The Jackson Laboratory
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|Allele Type||Gene Symbol||Gene Name|
|Targeted (Null/Knockout)||Rag1||recombination activating gene 1|
|Allele Type||Gene Symbol||Gene Name|
|Targeted (Null/Knockout)||Il2rg||interleukin 2 receptor, gamma chain|
These NRG mice are NOD-congenic mice harboring the Rag1null mutation (Rag1KO or Rag1tm1Mom) on chromosome 2 and the IL2rγnull mutation (IL2RγcKO or Il2rgtm1Wjl) on the X chromosome. These NRG mutant mice are also called NOD-Rag1null IL2rγnull double mutant mice or NOD.Rag1KO.IL2RγcKO mice. Females homozygous for both mutations (and males homozygous for Rag1null; hemizygous for the X-linked IL2rγnull mutation) are viable and fertile. When compared to NOD-scid IL2rgnull 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-Rag1null (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
These NRG mice are NOD-congenic mice harboring the Rag1null mutation (Rag1KO or Rag1tm1Mom) on chromosome 2 and the IL2rγnull mutation (IL2RγcKO or Il2rgtm1Wjl) on the X chromosome. These NRG mutant mice (also called NOD-Rag1null IL2rγnull double mutant mice or NOD.Rag1KO.IL2RγcKO mice) were produced by breeding NOD-Rag1null (Stock No. 003729) mice with NOD-scid IL2rgnull
(Stock No. 005557)
mice. Offspring were intercrossed and bred to be homozygous for the Rag1null mutation, homozygous (for females; or hemizygous for males) for the X-linked IL2rγnull 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.
|Allele Name||targeted mutation 1, Peter Mombaerts|
|Allele Type||Targeted (Null/Knockout)|
|Allele Synonym(s)||Rag1tm1Mom; 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+|
|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
|Allele Name||targeted mutation 1, Warren J Leonard|
|Allele Type||Targeted (Null/Knockout)|
|Allele Synonym(s)||Il2rgtm1Wjl; 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|
|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
When maintaining a live colony, females homozygous for both the Rag1null and IL2rγnull mutations may be bred with males homozygous for the Rag1null mutation and hemizygous for the X-linked IL2rγnull mutation. The donating investigator suggests that NOD.129S7(B6)-Rag1tm1Mom/J (Stock No. 003729), NOD/ShiLtJ (Stock No. 001976), or NOD/ShiLtSz may be appropriate controls.
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.
We will fulfill your order by providing at least two carriers for each strain ordered. The total number, sex, and genotypes provided will vary, although typically 8 or more animals are provided. Please check genotypes which will be recovered. While the genotypes of all animals produced will be communicated to you prior to scheduling shipment, the genotypes of animals provided may not reflect the mating scheme and genotypes described in the strain description. Animals are typically ready to ship in 11-14 weeks. If a second recovery is required to produce the minimum number of animals, then delivery time would increase to approximately 25 weeks. If we fail to produce animals of the correct genotype, you will not be charged. We cannot guarantee the reproductive success of mice shipped to your facility. If the mice are lost after the first three days (post-arrival) or do not produce progeny at your facility, a new order and fee will be necessary.
Cryorecovery to establish a Dedicated Supply for greater quantities of mice. Mice recovered can be used to establish a dedicated colony to contractually supply you mice according to your requirements. Price by quotation.
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