{{Short description|Immunodeficient laboratory mice brand}} The '''NSG mouse''' (NOD scid gamma mouse) is a brand of immunodeficient laboratory mice, developed and marketed by Jackson Laboratory, which carries the strain NOD.Cg-''Prkdc<sup>scid</sup> Il2rg<sup>tm1Wjl</sup>''/SzJ. NSG branded mice are among the most immunodeficient described to date.<ref name="pmid17259968">{{cite journal |vauthors=Shultz LD, Ishikawa F, Greiner DL |title=Humanized mice in translational biomedical research |journal=Nat. Rev. Immunol. |volume=7 |issue=2 |pages=118–130 |year=2007 |pmid=17259968 |doi=10.1038/nri2017 |s2cid=7933096 }}</ref> NSG branded mice lack mature T cells, B cells, and natural killer (NK) cells.<ref name="pmid15879151">{{cite journal |author=Shultz LD |title=Human lymphoid and myeloid cell development in NOD/LtSz-scid IL2R gamma null mice engrafted with mobilized human hemopoietic stem cells |journal=J. Immunol. |volume=174 |issue=10 |pages=6477–89 |year=2005 |pmid=15879151 |doi= 10.4049/jimmunol.174.10.6477|url= http://www.jimmunol.org/content/jimmunol/174/10/6477.full.pdf|name-list-style=vanc |author2=Lyons BL |author3=Burzenski LM |display-authors=3 |last4=Gott |first4=B |last5=Chen |first5=X |last6=Chaleff |first6=S |last7=Kotb |first7=M |last8=Gillies |first8=SD |last9=King |first9=M|doi-access=free |bibcode=2005JImm..174.6477S }}</ref> NSG branded mice are also deficient in multiple cytokine signaling pathways, and they have many defects in innate immunity.<ref name="pmid15879151" /><ref name="pmid7995938">{{cite journal |author=Shultz LD |title=Multiple defects in innate and adaptive immunologic function in NOD/LtSz-scid mice |journal=J. Immunol. |volume=154 |issue=1 |pages=180–91 |year=1995 |pmid=7995938 |name-list-style=vanc |author2=Schweitzer PA |author3=Christianson SW |display-authors=3 |last4=Gott |first4=B |last5=Schweitzer |first5=IB |last6=Tennent |first6=B |last7=McKenna |first7=S |last8=Mobraaten |first8=L |last9=Rajan |first9=TV |doi=10.4049/jimmunol.154.1.180 }}</ref> The compound immunodeficiencies in NSG branded mice permit the engraftment of a wide range of primary human cells, and enable sophisticated modeling of many areas of human biology and disease. NSG branded mice were developed in the laboratory of Dr. Leonard Shultz at Jackson Laboratory, which owns the NSG trade mark.

==Features of NSG mice== *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.<ref name="pmid7995938" /> 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.<ref name="pmid17982459">{{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 }}</ref> *The ''Prkdc<sup>scid</sup>'' mutation{{Ref|1|a}}, commonly known as "scid" or "severe combined immunodeficiency", essentially eliminates adaptive immunity.<ref name="pmid9617892">{{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 }}</ref> ''Prkdc<sup>scid</sup>'' 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.<ref name="pmid7889575">{{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 }}</ref> Mice homozygous for the mutation have severely reduced numbers of mature T and B cells.<ref name="pmid7995938" /><ref name="pmid9617892"/> The phenotypic penetrance of ''Prkdc<sup>scid</sup>'' varies among inbred strain backgrounds, but the mutation is most effective at eliminating adaptive immunity on the NOD genetic background.<ref name="pmid7995938" /> Due to the ''Prkdc<sup>scid</sup>'' 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.<ref name="Pearson">{{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}}</ref><ref name="Fulop">{{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}}</ref> *The ''Il2rg<sup>tm1Wjl</sup>'' 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).<ref name="pmid7697543">{{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 }}</ref> 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.<ref name="pmid7697543" /> Notably, the absence of IL2Rγ blocks NK cell differentiation, and thereby removes a major obstacle preventing the efficient engraftment of primary human cells.<ref name="pmid15879151" /><ref name="pmid9617892" />

==Research applications== *Primary human lung tumor xenografts that preserve the tumor microenvironment during long-term engraftment.<ref name="pmid18453623">{{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 }}</ref> *Humanized model for evaluation of possible cancer curing gene therapy.<ref name=" pmid = 20402329 ">{{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 | page = 217 | doi=10.1126/scitranslmed.3006353| s2cid = 8430299 | url-access = subscription }}</ref> *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<ref name="pmid19029987">{{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 }}</ref> and cancer stem cells.<ref name="pmid19052619">{{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 }}</ref> *Establishing a functional, humanized immune system from engrafted human hematopoietic stem cells<ref name="pmid15920010">{{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 }}</ref><ref name="pmid18653783">{{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. |doi-broken-date=13 April 2026 }}</ref> and progenitors.<ref name="pmid18371405">{{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 }}</ref> *Humanized models for studying human-specific infectious diseases like HIV,<ref name="pmid18691745">{{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}}</ref> Epstein Barr virus,<ref name="pmid19487422">{{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.}}</ref> malaria,<ref name="pmid19596869">{{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}}</ref> and Dengue fever.<ref name="pmid19535452">{{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}}</ref><ref name="pmid19802382">{{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 |article-number=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 }}</ref> Humanized models also aid in testing new therapies.<ref name="pmid18691745" /> *Studying allograft rejection after pancreatic islet transplantation therapy for type 1 diabetes.<ref name="pmid18096436">{{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.}}</ref>

== Animal model of skin transplantation == The development of an optimized NSG (NOD-scid IL2rynull) immunodeficient mouse model for human skin transplantation and the study of allograft rejection. The authors show that in NSG mice, human skin grafts are initially infiltrated by host murine Gr1+ myeloid cells, which impairs wound healing and the survival of human endothelium. However, injection of an anti-Gr1 antibody eliminates this infiltrate, improves graft healing, preserves human blood vessels, and allows the survival of passenger human leukocytes within the graft. These treated mice can then be injected with allogeneic human peripheral blood mononuclear cells (CD4+ or CD8+), which induces rapid and complete rejection of the skin graft, with destruction of the epidermis, endothelium, and dermal cells. This anti-Gr1-treated NSG model thus provides a valuable tool for studying the mechanisms of wound healing, revascularization, inflammation, and human allograft rejection.<ref>{{Cite journal |last1=Racki |first1=Waldemar J. |last2=Covassin |first2=Laurence |last3=Brehm |first3=Michael |last4=Pino |first4=Stephen |last5=Ignotz |first5=Ronald |last6=Dunn |first6=Raymond |last7=Laning |first7=Joseph |last8=Graves |first8=Susannah K. |last9=Rossini |first9=Aldo A. |last10=Shultz |first10=Leonard D. |last11=Greiner |first11=Dale L. |date=2010-03-15 |title=NOD-scid IL2rγnull Mouse Model of Human Skin Transplantation and Allograft Rejection |journal=Transplantation |language=en |volume=89 |issue=5 |pages=527–536 |doi=10.1097/TP.0b013e3181c90242 |pmid=20134397 |pmc=2901915 |issn=0041-1337}}</ref>

== Animal model of inflammatory bowel disease == The development and characterization of two humanized NSG (NOD/SCID/IL2rγnull) mouse models reconstituted with peripheral blood mononuclear cells (PBMCs) from patients with ulcerative colitis (NSG-UC) or Crohn's disease (NSG-CD), in order to better reflect the heterogeneity of inflammatory bowel diseases (IBD). In NSG-UC mice, ethanol challenge induces a strong pro-inflammatory response with edema, infiltration of CD4+ and CD8+ T cells, B cells, and monocytes into the mucosa, as well as moderate fibrosis. In contrast, NSG-CD mice spontaneously develop extensive fibrotic lesions, with collagen deposition between the muscular layers and fibroblast proliferation, without requiring chemical challenge. These models partially recapitulate the respective phenotypes of the two diseases, allow testing of therapeutics targeting human molecules, and may help stratify patients for personalized clinical trials.<ref>{{Cite journal |last1=Weß |first1=Veronika |last2=Schuster-Winkelmann |first2=Paula |last3=Karatekin |first3=Yasemin Hazal |last4=Malik |first4=Simge |last5=Beigel |first5=Florian |last6=Kühn |first6=Florian |last7=Gropp |first7=Roswitha |date=2023-08-02 |title=Humanized NSG Mouse Models as a Preclinical Tool for Translational Research in Inflammatory Bowel Diseases |journal=International Journal of Molecular Sciences |language=en |volume=24 |issue=15 |article-number=12348 |doi=10.3390/ijms241512348 |doi-access=free |pmid=37569722 |pmc=10418464 |issn=1422-0067}}</ref>

==References== {{reflist}}

==Notes== :1.{{Note|1}}[http://www.informatics.jax.org/javawi2/servlet/WIFetch?page=alleleDetail&key=1285 Mouse Genome Informatics entry for ''Prkdc<sup>scid</sup>''] :2.{{Note|2}}[http://www.informatics.jax.org/javawi2/servlet/WIFetch?page=alleleDetail&key=1656 Mouse Genome Informatics entry for ''Il2rg<sup>tm1Wjl</sup>'']

==External links== *[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