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

Stock number: 005557
Product name: NSG
Strain synonyms: NOD-scid IL2Rgamma^null, NOD-scid IL2Rg^null, NOD scid gamma
Research areas: Cancer Research, Immunology, Inflammation and Autoimmunity Research, Internal/Organ Research, Research Tools, Virology Research

Description

These mice are most often referred to using their branded name "NSG™" and are extremely immunodeficient. The mice carry two mutations on the NOD/ShiLtJ genetic background; severe combined immune deficiency (scid) and a complete null allele of the IL2 receptor common gamma chain (IL2rg^null). The scid mutation is in the DNA repair complex protein Prkdc and renders the mice B and T cell deficient. 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), peripheral blood mononuclear cells (PBMC), patient derived xenografts (PDX), or adult stem cells and tissues. The immunodeficient NSG mice enable research in human immune function, infectious disease, diabetes, oncology, and stem cell biology.

To order this model with CD34+ or PBMC engraftment, please visit our Humanized Mice page.

Detailed description

The NOD.Cg-Prkdc^scid Il2rg^tm1Wjl/SzJ mice, most often known by their branded name, NOD scid gamma (NSG™), do not express the Prkdc gene nor the X-linked Il2rg gene. NSG mice are viable, fertile, normal in size and do not display any gross physical or behavioral abnormalities. Histological examination of lymphoid tissues reveals absence of lymphoid cells and some cystic structures in the thymus, an absence of follicles in the spleen and markedly diminished celluarity of lymph nodes. NSG mice are deficient in mature lymphocytes, serum Ig is not detectable and natural killer (NK) cell cytotoxic activity is extremely low. These mice are resistant to lymphoma development even after sublethal irradiation treatment. These mutant mice have been shown to readily support engraftment of human CD34⁺ hematopoietic stem cells and represent a superior, long-lived model suitable for studies employing xenotransplantation strategies. NSG mice are highly sensitive to the diabetogenic effects of streptozotocin (STZ).

Kinked tail, head tilt, circling, and hind limb lameness are observed at low frequency. These conditions are very infrequent (<0.01% incidence) in young, experimentally naïve mice. Incidence is estimated at <0.5% in older mice used for humanization and other studies.

The NSG-STZ preclinical model for pancreatic islet transplantation is now available from JAX® Services.

Please note that the NSG 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.

View our Resources for the NSG™ mouse model, including,

• NSG™ Mouse Model Portfolio
• Housing and Breeding Considerations for NSG™ Mice
• Frequently Asked NSG™ Questions
• Breakthrough Research Using NSG™
• Immunodeficient Mouse and Xenograft Host Comparisons
• Flow Cytometry Characterization Data for Immunodeficient JAX Strains

Development

These double mutant mice were produced by breeding female NOD.CB17-Prkdc^scid/J (Stock No. 001303) mice with male mice bearing the X-linked B6.129S4-Il2rg^tm1Wjl/J allele (Stock No. 003174). The resulting male mice heterozygous for the Prkdc^scid allele and hemizygous for the Il2rg^tm1Wjl allele were crossed to female NOD.CB17-Prkdc^scid/J (Stock No. 001303) mice for eight generations. Heterozygotes were interbred to produce mice homozygous for the Prkdc^scid allele and homozygous (females) or hemizygous (males) for the Il2rg^tm1Wjl allele.

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.