NRG mice

NRG mice

NRG mice

Strain details
Nomenclature NOD.Cg-Rag1 tm1MomI l2rg tm1Wjl /SzJ/Ozarc
StrainCongenic, Targeted (Null/Knockout)
Common nameNRG
SynonymsNOD-Rag1null IL2rgnull, NOD rag gamma, NOD-RG
Coat colourAlbino (A/A Tyrc/Tyrc)
SpeciesMouse
Genetic backgroundNOD/ShiLtJ
JAX stock number007799
LocationArea Oz1
Weekly wean target15 males,100 females

Strain description

  • MHC Haplotype: H2Kg7
  • NRG mice are NOD-congenic mice harbouring the Rag1null mutation (Rag1KO or Rag1tm1Mom) on chromosome 2 and the IL2rγnull mutation (IL2RγcKO or Il2rgtm1Wjl) on the X chromosome.
  • They may also be referred to as NOD-Rag1null IL2rγnull double mutant mice or NOD.Rag1KO.IL2RγcKO mice. Females that are homozygous for both mutations, as well as males homozygous for Rag1null and hemizygous for the X-linked IL2rγnull mutation, are both viable and fertile.
  • This stock strain can tolerate much higher levels of irradiation conditioning than NOD-scid IL2rgnull (NSG) mice.
  • 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 (Jax No. 003729) or NOD-scid (Jax No.001303) mice.
  • To accommodate their level of immunodeficiency, NRG mice are maintained at Ozgene ARC in a maximum barrier environment, housed within individually ventilated cages (IVC).
  • 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.
  • 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.

Past ARC and transfer reports:

Current Ozgene ARC reports (from 01-Jun-2023)

  • Mouse images are representative only. Actual phenotypes may vary based on genotype, sex, age, husbandry, health status, and other factors.
  • Pearson T, et al. Clin Exp Immunol. 2008 Nov; 154(2): 270–284. PMID: 18785974 doi: 10.1111/j.1365-2249.2008.03753.x Non-obese diabetic–recombination activating gene-1 (NOD–Rag 1 null ) interleukin (IL)- 2 receptor common gamma chain (IL 2 rγ null ) null mice: a radioresistant model for human lymphohaematopoietic engraftment.
  • Mombaerts P, et al. Cell. 1992 Mar 6;68(5):869-77.  PMID: 1547488
    doi: 10.1016/0092-8674(92)90030-g. RAG-1-deficient mice have no mature B and T lymphocytes.
  • 3. Kitsera M, et al. Viruses. 2023 Feb; 15(2): 478. PMID: 36851692 doi: 10.3390/v15020478 Recent Developments in NSG and NRG Humanized Mouse Models for Their Use in Viral and Immune Research.
  • Brehm MA, Cuthbert A, Yang C, Miller DM, DiIorio P, Laning J, Burzenski L, Gott B, Foreman O, Kavirayani A, Herlihy M, Rossini AA, Shultz LD, Greiner DL. Parameters for establishing humanized mouse models to study human immunity: analysis of human hematopoietic stem cell engraftment in three immunodeficient strains of mice bearing the IL2rgamma(null) mutation. Clin Immunol. 2010 Apr;135(1):84-98. doi: 10.1016/j.clim.2009.12.008. Epub 2010 Jan 21. PMID: 20096637; PMCID: PMC2835837.
  • 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. 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. 2008 Nov;154(2):270-84. doi: 10.1111/j.1365-2249.2008.03753.x. Epub 2008 Sep 8. PMID: 18785974; PMCID: PMC2612717.
  • More info https://www.jax.org/strain/007799

NRG mice

The NRG strain is immunodeficient, radioresistant, non-obese diabetic (NOD) stock mice. It carries two mutations on the NOD/ShiLtJ genetic background; a targeted knockout mutation in recombination activating gene-1 (Rag1null) and a complete knockout allele of the interleukin (IL)-2 receptor common gamma chain (IL2rγnull).

  • The Rag1null mutation mice are lack of mature B and T lymphocytes due to an early block in differentiation, resembling the immune system of nonleaky scid mice but without neuroanatomical or behavioural defects.
  • The IL2rgnull mutation is a knockout mutation of the gene encoding the gamma c chain to interleukins, prevents cytokine signalling through multiple receptors, leading to a deficiency in functional Natural Killer (NK) cells.

A combination of these two mutations induces severe immunodeficiency, which allows the mice to be humanized by engraftment with human CD34+ hematopoietic stem cells (HSC) and patient-derived xenografts (PDX) at high efficiency.

The immunodeficient NOD–Rag1null IL2rγnull mice tolerate much higher levels of irradiation conditioning and genotoxic drugs than mice with a scid mutation in the DNA repair enzyme Prkdc (NSG).

Application and research

NRG mice are used in cancer research and particularly valuable in translational research, where findings are intended to be directly applied to developing treatments for human diseases. Their use has significantly advanced the field of oncology by providing deeper insights into cancer biology and treatment. Here are some main application and research fields utilising NRG mice.

  • Xenograpft and Patient-Derived Xenograph (PDX) models: NRG mice are widely used for engrafting human tumours to create models that closely mimic human cancer. These models are crucial for studying tumour biology, progression and the response to therapeutics in a context that closely resembles that clinical scenario.
  • Tumour Microenvironment Studies: these mice are used to analyse how the tumour microenvironment influences cancer progression and response to therapy. Since NRG mice have a compromised immune system, they allow the human tumour cells to interact more naturally with the surrounding tissues without being rejected.
  • Immunotherapy Development: Despite their immunodeficiency, MRG mice can be used to test the efficacy of certain types of immunotherapies especially when human immune cells are also transplanted to create humanised immune system within the mouse. This allows researchers to observe how human immune cells respond to cancer therapies in a controlled environment.
  • Human Immune System Reconstitution: NRG mice can be engrafted with human hematopoietic stem cells (HSCs) to develop a human-like immune system. This makes them valuable for studying human immune system responses and diseases in a living organism.
  • Study of Infection Diseases: With their humanised immune system, MRG mice serve as models for studying infection diseases that specifically interact with human immune cells providing insights into pathogenesis and potential treatments.
  • Gene Function Studies: Researchers use NRG mice to understand the role of specific human gene especially those related to the immune system by observing how their expression influences disease progression and treatment response.
  • Pharmacology and Toxicology: NRG mice are used to evaluate the pharmacodynamics and toxicology of new drugs, particularly cancer therapies to assess their safety and efficacy before clinical trials.