NSG-Hprtnull mice are NOD.scid.Il2Rγcnull ("NSG") animals with the Hprtnull knockout allele. The NSG model is permissive for xenograft/human tumor growth, with Hprt-deficiency allowing human tumors to be transplanted into culture and any mouse cells removed (via HAT selection).
Michael Wiles, The Jackson Laboratory
Genetic Background | Generation |
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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 |
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Targeted (Null/Knockout) | Il2rg | interleukin 2 receptor, gamma chain |
Allele Type | Gene Symbol | Gene Name |
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Endonuclease-mediated (Null/Knockout) | Hprt | hypoxanthine guanine phosphoribosyl transferase |
NSG-Hprtnull mice are NOD.scid.Il2Rγcnull ("NSG"; Stock No. 005557) animals also harboring the Hprtem1Mvw allele (Hprtnull). The Hprtnull mutation has as a frame shift and premature termination, resulting in function knockout. Hprt-deficiency causes hypoxanthine-aminopterin-thymidine (HAT)-inducible cell death, but renders the cell resistant to 6-thioguanine (6-TG) cytotoxicity.
NSG-Hprtnull females homozygous for all three mutations, and males that are homozygous for scid and hemizygous for the X-linked mutations Hprtnull and Il2Rγcnull, may be collectively referred to as homozygous NSG-Hprtnull mice.
These NSG-Hprtnull mice may be expected to have a similar phenotype as the NSG-Hprtb-m3 model (Stock No. 012480) that has the Hprtb-m3 knockout rather than the Hprtem1Mvw knockout. The expected phenotype of NSG-Hprtnull mice is described below.
Although viable and fertile, homozygous NSG-Hprtnull mice are immunodeficient: they have no mature T cells or B cells, lack functional natural killer (NK) cells, have reduced numbers of lymphocytes and myeloid dendritic cells, and are deficient in cytokine signaling. The Hprt-deficiency results in biochemically defective stromal cells.
Like homozygous NSG mice, homozygous NSG-Hprtnull mice are designed to allow engraftment of human tissues and primary cancers, such as hematopoietic cancers (e.g., leukemia), melanoma, ER+ breast cancer xenografts, purified human CD4+ T cells (fractionated from human peripheral blood mononuclear cells [PBMC]), and other tissues. When human cancers are implanted in Hprt-deficient NSG mice, the mouse fibroblast and stromal cells replace the human stromal cells. Following tumor explantation into culture, any Hprt-deficient mouse cells can be eliminated by HAT selection; resulting in isolation of human cancer cells. Conversely, Hprt-deficient mouse cells can be enriched by 6-TG selection. These mice may be used to generate patient-specific low passage cell lines from primary cancers for use in chemosensitivity profiling and other applications.
Similar to other immunodeficient strains, maintaining homozygous NSG-Hprtnull mice in high health status (specific pathogen-free) vivaria promotes overall colony health. If homozygous NSG-Hprtnull animals are maintained in low health barrier rooms, the use of medicated water (e.g., sulfatrim/trimethoprim-sulfa or enrofloxacin/Baytril) is suggested to increase overall colony health.
View our Resources for the NSG mouse model, including discussion forum, immunodeficient model comparison, and categorized, up-to-date references.
NSG-Hprtnull mice are NOD.scid.Il2Rγcnull ("NSG") animals with the Hprtem1Mvw knockout allele (Hprtnull). NSG-Hprtnull mice harbor several mutations, as described below.
NSG mice are non-obese diabetic animals (NOD/ShiLtJ) harboring the spontaneous severe combined immunodeficiency mutation (Prkdcscid) on chromosome 16 and the Il2Rγcnull mutation at ~101 Mbp on the X chromosome (Il2rgtm1Wjl created by Dr. Warren J. Leonard [NIH]). NSG mice are described and available from The Jackson Laboratory Repository as Stock No. 005557.
The Hprtem1Mvw knockout allele (Hprtnull) was created by Dr. Michael V. Wiles (The Jackson Laboratory) using CRISPR/Cas9 genome engineering in NSG mouse zygotes (Stock No. 005557). The hypoxanthine guanine phosphoribosyl transferase locus (Hprt) on the X chromosome (~53 Mbp) was targeted with a specific single guide RNA (sgRNA) to create an 18 bp deletion, resulting in a frame shift and premature termination. The founder mouse was bred to NSG mice, and the offspring were bred together to produce homozygous mice.
In 2014, Dr. Wiles sent NSG-Hprtnull triple mutant mice to The Jackson Laboratory Repository as Stock No. 026222. The colony is maintained by breeding females homozygous for all three mutations with males that are homozygous for scid and hemizygous for the X-linked mutations Hprtnull and Il2Rγcnull.
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, 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 |
Allele Name | endonuclease-mediated mutation 1, Michael Wiles |
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Allele Type | Endonuclease-mediated (Null/Knockout) |
Allele Synonym(s) | Hprtnull |
Gene Symbol and Name | Hprt, hypoxanthine guanine phosphoribosyl transferase |
Gene Synonym(s) | |
Strain of Origin | NOD.Cg-Prkdcscid Il2rgtm1Wjl/SzJ |
Chromosome | X |
Molecular Note | This allele was generated by injecting Cas9 RNA and a specific single guide RNA (sgRNA) to create an 18 bp deletion, resulting in a frame shift and premature termination. |
NSG-Hprtnull females homozygous for all three mutations, and males that are homozygous for scid (Prkdcscid) and hemizygous for the X-linked mutations Hprtem1Mvw (Hprtnull) and Il2Rγcnull (Il2rgtm1Wjl) may be collectively referred to as homozygous NSG-Hprtnull mice.
When maintaining a live colony, homozygous NSG-Hprtnull females may be bred with homozygous NSG-Hprtnull males.
Homozygous NSG-Hprtnull mice are immunodeficient. As such, and similar to other immunodeficient strains, maintenance in high health status (specific pathogen-free) vivaria promotes overall colony health. If homozygous NSG-Hprtnull animals are maintained in low health barrier rooms, the use of medicated water (e.g., sulfatrim/trimethoprim-sulfa or enrofloxacin/Baytril) is suggested to increase overall colony health. Also see additional NSG housing information.
When using the NOD.Cg-Prkdcscid Hprtem1Mvw Il2rgtm1Wjl/MvwJ mouse strain in a publication, please cite the originating article(s) and include JAX stock #026222 in your Materials and Methods section.
Facility Barrier Level Descriptions
Service/Product | Description | Price |
---|---|---|
Homozygous forPrkdc<scid> and Hprt<em1Mvw>, Homozygous females and Hemizygous males for Il2rg<tm1Wjl>, |
Frozen Mouse Embryo | NOD.Cg-Prkdc<scid> Hprt<em1Mvw> Il2rg<tm1Wjl> Frozen Embryos | $2595.00 |
Frozen Mouse Embryo | NOD.Cg-Prkdc<scid> Hprt<em1Mvw> Il2rg<tm1Wjl> Frozen Embryos | $2595.00 |
Frozen Mouse Embryo | NOD.Cg-Prkdc<scid> Hprt<em1Mvw> Il2rg<tm1Wjl> Frozen Embryos | $3373.50 |
Frozen Mouse Embryo | NOD.Cg-Prkdc<scid> Hprt<em1Mvw> Il2rg<tm1Wjl> Frozen Embryos | $3373.50 |
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