NSG mouse

• The genetic background, derived from inbred NOD mouse strain NOD/ShiLtJ, contributes reductions in innate immunity that include an absent hemolytic complement system, reduced dendritic cell function, and defective macrophage activity. The NOD/ShiLtJ background also contributes an allele of the Sirpa gene that renders the bone marrow niche very permissive to colonization by human hematopoietic stem cells.{{cite journal |author=Takenaka K |title=Polymorphism in Sirpa modulates engraftment of human hematopoietic stem cells |journal=Nat. Immunol. |volume=8 |issue=12 |pages=1313–23 |year=2007 |pmid=17982459 |doi=10.1038/ni1527 |name-list-style=vanc |author2=Prasolava TK |author3=Wang JC |display-authors=3 |last4=Mortin-Toth |first4=Steven M |last5=Khalouei |first5=Sam |last6=Gan |first6=Olga I |last7=Dick |first7=John E |last8=Danska |first8=Jayne S|s2cid=7874854 }}
• The Prkdc^scid mutation{{Ref|1|a}}, commonly known as “scid” or “severe combined immunodeficiency”, essentially eliminates adaptive immunity.{{cite journal |vauthors=Greiner DL, Hesselton RA, Shultz LD |title=SCID mouse models of human stem cell engraftment |journal=Stem Cells |volume=16 |issue=3 |pages=166–177 |pmid=9617892 |doi=10.1002/stem.160166 |year=1998|doi-access=free }} Prkdc^scid is a loss-of-function mutation in the mouse homologue of the human PRKDC gene, which encodes a protein that resolves DNA strand breaks that occur during V(D)J recombination in developing T and B lymphocytes.{{cite journal |author=Blunt T |title=Defective DNA-dependent protein kinase activity is linked to V(D)J recombination and DNA repair defects associated with the murine scid mutation |journal=Cell |volume=80 |issue=5 |pages=813–23 |year=1995 |pmid=7889575 |doi= 10.1016/0092-8674(95)90360-7|name-list-style=vanc |author2=Finnie NJ |author3=Taccioli GE |display-authors=3 |last4=Smith |first4=GC |last5=Demengeot |first5=J |last6=Gottlieb |first6=TM |last7=Mizuta |first7=R |last8=Varghese |first8=AJ |last9=Alt |first9=FW|doi-access=free }} Mice homozygous for the mutation have severely reduced numbers of mature T and B cells. The phenotypic penetrance of Prkdc^scid varies among inbred strain backgrounds, but the mutation is most effective at eliminating adaptive immunity on the NOD genetic background. Due to the Prkdc^scid mutation, however, the NSG strain shows high sensitivity to radiation, T-cell leakage, and increased incidence of thymic lymphoma formation; as such, this strain cannot be used to predict clinical response to certain anticancer drugs, or for long-term transplantation studies.{{cite journal|last1=Pearson|first1=T|last2=Shultz|first2=LD|year=2008|title=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|journal=Clinical & Experimental Immunology|volume=154|issue=2|pages=270–284|doi=10.1111/j.1365-2249.2008.03753.x|pmid=18785974|pmc=2612717}}{{cite journal|last1=Fulop|first1=GM|last2=Phillips|first2=RA|year=1990|title=The Scid Mutation in Mice Causes a General Defect in DNA Repair|journal=Nature|volume=347|issue=6292|pages=479–482|doi=10.1038/347479a0|pmid=2215662|bibcode=1990Natur.347..479F|s2cid=4351206}}
• The Il2rg^tm1Wjl targeted mutation{{Ref|2|b}} is a complete null mutation in the gene encoding the interleukin 2 receptor gamma chain (IL2Rγ, homologous to IL2RG in humans).{{cite journal |author=Cao X |title=Defective lymphoid development in mice lacking expression of the common cytokine receptor gamma chain |journal=Immunity |volume=2 |issue=3 |pages=223–38 |year=1995 |pmid=7697543 |doi= 10.1016/1074-7613(95)90047-0|name-list-style=vanc |author2=Shores EW |author3=Hu-Li J |display-authors=3 |last4=Anver |first4=MR |last5=Kelsall |first5=BL |last6=Russell |first6=SM |last7=Drago |first7=J |last8=Noguchi |first8=M |last9=Grinberg |first9=A|doi-access=free }} IL2Rγ is a common component of the cell surface receptors that bind and transduce signals from six distinct interleukins. Signaling through IL2Rγ is required for the differentiation and function of many hematopoietic cells. Notably, the absence of IL2Rγ blocks NK cell differentiation, and thereby removes a major obstacle preventing the efficient engraftment of primary human cells.

• Primary human lung tumor xenografts that preserve the tumor microenvironment during long-term engraftment.{{cite journal |author=Simpson-Abelson MR |title=Long-term engraftment and expansion of tumor-derived memory T cells following the implantation of non-disrupted pieces of human lung tumor into NOD-scid IL2Rgamma(null) mice |journal=J. Immunol. |volume=180 |issue=10 |pages=7009–18 |year=2008 |pmid=18453623 |doi= 10.4049/jimmunol.180.10.7009|name-list-style=vanc |author2=Sonnenberg GF |author3=Takita H |display-authors=3 |last4=Yokota |first4=SJ |last5=Conway Jr |first5=TF |last6=Kelleher Jr |first6=RJ |last7=Shultz |first7=LD |last8=Barcos |first8=M |last9=Bankert |first9=RB|doi-access=free }}
• Humanized model for evaluation of possible cancer curing gene therapy.{{cite journal |vauthors=Escobar G, Moi D, Ranghetti A, etal | title = Genetic engineering of hematopoiesis for targeted IFN-α delivery inhibits breast cancer progression. | journal = Sci. Transl. Med. | volume = 6 | issue = 217 |date=Jan 2014 | pmid = 24382895 | url = https://www.science.org/doi/abs/10.1126/scitranslmed.3006353 | pages = 217 | doi=10.1126/scitranslmed.3006353| s2cid = 8430299 }}
• Models of acute or chronic leukemia established using cancer cells collected from patients.{{Citation needed|date=June 2024}}
• A highly sensitive platform for studying epithelial{{cite journal |author=Eirew P |title=A method for quantifying normal human mammary epithelial stem cells with in vivo regenerative ability |journal=Nat. Med. |volume=14 |issue=12 |pages=1384–9 |year=2008 |pmid=19029987 |doi=10.1038/nm.1791 |name-list-style=vanc |author2=Stingl J |author3=Raouf A |display-authors=3 |last4=Turashvili |first4=Gulisa |last5=Aparicio |first5=Samuel |last6=Emerman |first6=Joanne T |last7=Eaves |first7=Connie J|s2cid=205385845 }} and cancer stem cells.{{cite journal |vauthors=Quintana E, Shackleton M, Sabel MS, Fullen DR, Johnson TM, Morrison SJ |title=Efficient tumour formation by single human melanoma cells |journal=Nature |volume=456 |issue=7222 |pages=593–598 |year=2008 |pmid=19052619 |pmc=2597380 |doi=10.1038/nature07567 |bibcode=2008Natur.456..593Q }}
• Establishing a functional, humanized immune system from engrafted human hematopoietic stem cells{{cite journal |vauthors=Ishikawa F, Yasukawa M, Lyons B, etal |title=Development of functional human blood and immune systems in NOD/SCID/IL2 receptor {gamma} chain(null) mice |journal=Blood |volume=106 |issue=5 |pages=1565–73 |year=2005 |pmid=15920010 |pmc=1895228 |doi=10.1182/blood-2005-02-0516 }}{{cite journal |author=Giassi LJ |title=Expanded CD34+ human umbilical cord blood cells generate multiple lymphohematopoietic lineages in NOD-scid IL2rgamma(null) mice |journal=Exp. Biol. Med. (Maywood) |volume=233 |issue=8 |pages=997–1012 |date=August 2008 |pmid=18653783 |pmc=2757278 |doi=10.3181/0802-RM-70 |name-list-style=vanc |author2=Pearson T |author3=Shultz LD |display-authors=3 |last4=Laning |first4=J. |last5=Biber |first5=K. |last6=Kraus |first6=M. |last7=Woda |first7=B. A. |last8=Schmidt |first8=M. R. |last9=Woodland |first9=R. T.}} and progenitors.{{cite journal |vauthors=Majeti R, Park CY, Weissman IL |title=Identification of a hierarchy of multipotent hematopoietic progenitors in human cord blood |journal=Cell Stem Cell |volume=1 |issue=6 |pages=635–645 |year=2007 |pmid=18371405 |pmc=2292126 |doi=10.1016/j.stem.2007.10.001 }}
• Humanized models for studying human-specific infectious diseases like HIV,{{cite journal |author=Kumar P |title=T cell-specific siRNA delivery suppresses HIV-1 infection in humanized mice |journal=Cell |volume=134 |issue=4 |pages=577–86 |year=2008 |pmid=18691745 |doi=10.1016/j.cell.2008.06.034 |name-list-style=vanc |author2=Ban HS |author3=Kim SS |display-authors=3 |last4=Wu |first4=Haoquan |last5=Pearson |first5=Todd |last6=Greiner |first6=Dale L. |last7=Laouar |first7=Amale |last8=Yao |first8=Jiahong |last9=Haridas |first9=Viraga |pmc=2943428}} Epstein Barr virus,{{cite journal |author=Strowig T |title=Priming of protective T cell responses against virus-induced tumors in mice with human immune system components |journal=J. Exp. Med. |volume=206 |issue=6 |pages=1423–34 |year=2009 |pmid=19487422 |pmc=2715061 |doi=10.1084/jem.20081720 |name-list-style=vanc |author2=Gurer C |author3=Ploss A |display-authors=3 |last4=Liu |first4=Y.-F. |last5=Arrey |first5=F. |last6=Sashihara |first6=J. |last7=Koo |first7=G. |last8=Rice |first8=C. M. |last9=Young |first9=J. W.}} malaria,{{cite journal |author=Jiménez-Díaz MB |title=Improved murine model of malaria using Plasmodium falciparum competent strains and non-myelodepleted NOD-scid IL2Rgammanull mice engrafted with human erythrocytes |journal=Antimicrob. Agents Chemother. |volume=53 |issue=10 |pages=4533–6 |year=2009 |pmid=19596869 |doi=10.1128/AAC.00519-09 |name-list-style=vanc |author2=Mulet T |author3=Viera S |display-authors=3 |last4=Gomez |first4=V. |last5=Garuti |first5=H. |last6=Ibanez |first6=J. |last7=Alvarez-Doval |first7=A. |last8=Shultz |first8=L. D. |last9=Martinez |first9=A. |pmc=2764183}} and Dengue fever.{{cite journal |vauthors=Mota J, Rico-Hesse R |title=Humanized mice show clinical signs of dengue fever according to infecting virus genotype |journal=J. Virol. |volume=83 |issue=17 |pages=8638–8645 |year=2009 |pmid=19535452 |doi=10.1128/JVI.00581-09 |pmc=2738212}}{{cite journal |author=Jaiswal S |title=Dengue virus infection and virus-specific HLA-A2 restricted immune responses in humanized NOD-scid IL2rgammanull mice |journal=PLOS ONE |volume=4 |issue=10 |pages=e7251 |year=2009 |pmid=19802382 |pmc=2749937 |doi=10.1371/journal.pone.0007251 |name-list-style=vanc |author2=Pearson T |author3=Friberg H |display-authors=3 |editor1-last=Unutmaz |editor1-first=Derya |last4=Shultz |first4=Leonard D. |last5=Greiner |first5=Dale L. |last6=Rothman |first6=Alan L. |last7=Mathew |first7=Anuja|bibcode=2009PLoSO...4.7251J |doi-access=free }} Humanized models also aid in testing new therapies.
• Studying allograft rejection after pancreatic islet transplantation therapy for type 1 diabetes.{{cite journal |author=King M |title=A new Hu-PBL model for the study of human islet alloreactivity based on NOD-scid mice bearing a targeted mutation in the IL-2 receptor gamma chain gene |journal=Clin. Immunol. |volume=126 |issue=3 |pages=303–14 |year=2008 |pmid=18096436 |doi=10.1016/j.clim.2007.11.001 |name-list-style=vanc |author2=Pearson T |author3=Shultz LD |display-authors=3 |last4=Leif |first4=Jean |last5=Bottino |first5=Rita |last6=Trucco |first6=Massimo |last7=Atkinson |first7=Mark A. |last8=Wasserfall |first8=Clive |last9=Herold |first9=Kevan C.}}

{{reflist}}

:1.{{Note|1}}[http://www.informatics.jax.org/javawi2/servlet/WIFetch?page=alleleDetail&key=1285 Mouse Genome Informatics entry for Prkdc^scid]

:2.{{Note|2}}[http://www.informatics.jax.org/javawi2/servlet/WIFetch?page=alleleDetail&key=1656 Mouse Genome Informatics entry for Il2rg^tm1Wjl]

• [http://jaxmice.jax.org/strain/005557.html NSG strain datasheet at The Jackson Laboratory]
• [http://community.jax.org/forums/5.aspx NSG discussion forum]
• [http://jaxmice.jax.org/research/immunology/005557-references.html Categorized list of references]

Category:Immunology mice