NOD.Cg-Rag1^tm1Mom Il2rg^tm1Wjl/SzJ

Stock number: 007799
Product name: NRG
Strain synonyms: NOD-Rag1^null IL2rg^null, NOD rag gamma
Research areas: Cancer Research, Hematological Research, Immunology, Inflammation and Autoimmunity Research, Internal/Organ Research, Research Tools

Description

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.

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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.

Allele

Symbol: Rag1^tm1Mom
Name: targeted mutation 1, Peter Mombaerts
MGI accession ID: MGI:1857241
Generation method: Targeted
Attributes: Null/Knockout
Marker symbol: Rag1
Marker name: recombination activating gene 1
Chromosome: 2
Strain of origin: 129S7/SvEvBrd-Hprt⁺
Site of expression: expression is seen in bone marrow derived cell lines.
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.

Allele

Symbol: Il2rg^tm1Wjl
Name: targeted mutation 1, Warren J Leonard
MGI accession ID: MGI:1857455
Generation method: Targeted
Attributes: Null/Knockout
Marker symbol: Il2rg
Marker name: interleukin 2 receptor, gamma chain
Chromosome: X
Strain of origin: 129S4/SvJae
Site of expression: Primarily lymphoid cells.
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.