NOD.Cg-B2m^tm1Unc Prkdc^scid Il2rg^tm1Wjl/SzJ

Stock number: 010636
Product name: NSG B2m
Strain synonyms: NOD-scid Il2rg<null> B2m<null>, NOD-scid gamma B2m, NSG-B2m KO
Research areas: Cancer Research, Hematological Research, Immunology, Inflammation and Autoimmunity Research, Internal/Organ Research, Metabolism Research, Research Tools, Virology Research

Description

These NOD scid Il2ry^null B2m^null 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).

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Detailed description

The NOD.Cg-Prkdc^scid B2m^tm1Unc Il2rg^tm1Wjl/SzJ mice, commonly known as NOD-scid Il2ry^null 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 Il2ry^null B2m^null 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 Il2ry^null treated similarly. The blood of GVHD affected NOD-scid Il2ry^null B2m^null 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 Il2ry^null. 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.

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Development

Triple mutant mice were produced by breeding NOD/LtSz-Prkdc^scid B2m^tm1Unc/Sz (Stock No. 003449) mice with NOD.Cg-Prkdc^scid Il2rg^tm1Wjl/Sz (Stock No. 5557) mice. The resulting mice were interbred to produce mice homozygous for the Prkdc^scid and B2m^tm1Unc alleles and homozygous (females) or hemizygous (males) for the X-linked Il2rg^tm1Wjl allele. The T1DR received this stock in 2009.

Allele

Symbol: B2m^tm1Unc
Name: targeted mutation 1, University of North Carolina
MGI accession ID: MGI:1857133
Generation method: Targeted
Attributes: Null/Knockout
Marker symbol: B2m
Marker name: beta-2 microglobulin
Chromosome: 2
Strain of origin: 129P2/OlaHsd
Molecular note: Insertion of a neomycin-resistance gene into the second exon.

Allele

Symbol: Prkdc^scid
Name: severe combined immunodeficiency
MGI accession ID: MGI:1857113
Generation method: Spontaneous
Marker symbol: Prkdc
Marker name: protein kinase, DNA activated, catalytic polypeptide
Chromosome: 16
Strain of origin: C.BKa-Igh^b/Icr
Site of expression: T and B lymphocytes.
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

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.