These NOD scid Il2rynull B2mnull triple mutant mice combine the features of the severe combined immune deficiency mutation (scid), IL2 receptor gamma chain deficiency, and the MHC class I molecule (beta-2 microglobulin) deficiency and are relatively resistant to graft versus host disease (GVHD). They provide a model useful to study in vivo mechanisms of xenogeneic GVHD and to rapidly assess therapeutic agents.
The serum half-life of human IgG is greatly reduced in B2m mutant strains due to defective FcRn function (Junghans and Anderson, 1996, Praetor and Hunziker, 2002).
Dr. Leonard D. Shultz, The Jackson Laboratory
Genetic Background | Generation |
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005557 NOD.Cg-Prkdcscid Il2rgtm1Wjl/SzJ |
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Allele Type | Gene Symbol | Gene Name |
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Spontaneous | Prkdc | protein kinase, DNA activated, catalytic polypeptide |
Allele Type | Gene Symbol | Gene Name |
---|---|---|
Targeted (Null/Knockout) | B2m | beta-2 microglobulin |
Allele Type | Gene Symbol | Gene Name |
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Targeted (Null/Knockout) | Il2rg | interleukin 2 receptor, gamma chain |
The NOD.Cg-Prkdcscid B2mtm1Unc Il2rgtm1Wjl/SzJ mice, commonly known as NOD-scid Il2rynull B2m null (NSG-B2m), do not express the Prkdc gene, the X-linked Il2rg gene nor the B2m gene. Triple mutant mice are viable, normal in size and do not display any gross physical or behavioral abnormalities, but can be poor breeders. Mutant mice combine the features of the NOD/ShiLtJ background, the severe combined immune deficiency mutation (scid), IL2 receptor gamma chain deficiency and the MHC class I molecule, beta-2 microglobulin, deficiency and are relatively resistant to graft versus host disease (GVHD). The mean survival time (MST) of NOD-scid Il2rynull B2mnull irradiated with 2 Gy and injected with 5 x 106 human peripheral blood mononuclear cells (PBMC) is 44 days compared to the MST of 21 days in the NOD-scid Il2rynull treated similarly. The blood of GVHD affected NOD-scid Il2rynull B2mnull animals exhibited decreased human CD45+ cell engraftment and significantly higher CD4:Cd8 ratios in spleen and bone marrow when compared with GVHD affected NOD-scid Il2rynull. This model may be useful to study in vivo mechanisms of xenogeneic graft versus host disease and to rapidly assess therapeutic agents.
Please note that this strain carries the true null interleukin-2 receptor gamma chain mutation and should not be confused with other strains that express a truncated interleukin-2 receptor gamma chain as described in: "Modulation of hematopoiesis in mice with a truncated mutant of the interleukin-2 receptor gamma chain" Ohbo K, et al. Blood 1996. 87:956-67.
Triple mutant mice were produced by breeding NOD/LtSz-Prkdcscid B2mtm1Unc/Sz (Stock No. 003449) mice with NOD.Cg-Prkdcscid Il2rgtm1Wjl/Sz (Stock No. 5557) mice. The resulting mice were interbred to produce mice homozygous for the Prkdcscid and B2mtm1Unc alleles and homozygous (females) or hemizygous (males) for the X-linked Il2rgtm1Wjl allele. The T1DR received this stock in 2009.
Allele Name | severe combined immunodeficiency |
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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-Ighb/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*). |
Allele Name | targeted mutation 1, University of North Carolina |
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Allele Type | Targeted (Null/Knockout) |
Allele Synonym(s) | b2mnull; beta2M-; beta2m0; beta2mnull; beta2mo; beta2mtm1Unc; beta2MKO; beta2-m-KO; I0; MHC-I- |
Gene Symbol and Name | B2m, beta-2 microglobulin |
Gene Synonym(s) | |
Strain of Origin | 129P2/OlaHsd |
Chromosome | 2 |
Molecular Note | Insertion of a neomycin-resistance gene into the second exon. |
Mutations Made By | Dr. Oliver Smithies, University of North Carolina at Chapel Hill |
Allele Name | targeted mutation 1, Warren J Leonard |
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Allele Type | Targeted (Null/Knockout) |
Allele Synonym(s) | [KO]gammac; CD132-; gammac-; gc-; Il2rgtm1Wjll; IL2Rgammanull |
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 |
When maintaining a live colony, these mice can be bred by crossing female mice that are heterozygous for the B2mtm1Unc allele and homozygous for the Prkdcscid allele, and homozygous for the X-linked Il2rgtm1Wjl allele to male mice that are homozygous for the B2mtm1Unc and Prkdcscid alleles and hemizygous for the X-linked Il2rgtm1Wjl allele.
Related Genotype: A/A Tyrc/Tyrc
When using the NSG B2m mouse strain in a publication, please cite the originating article(s) and include JAX stock #010636 in your Materials and Methods section.
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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.
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