JAX Mouse Strain Datasheet - 013062

NOD.Cg-Prkdc^scid Il2rg^tm1Wjl Tg(CMV-IL3,CSF2,KITLG)1Eav/MloySzJ

Stock No:: 013062 |; NSG-SGM3

Readily Available

Overview

Also Known As: NOD-scid IL2Rgnull-3/GM/SF, NSG-SGM3, NSGS

The triple transgenic NSG-SGM3 (NSGS) mice expressing human IL3, GM-CSF and SCF combine the features of the highly immunodeficient NOD scid gamma (NSG) mouse with cytokines that support the stable engraftment of myeloid lineages and regulatory T cell populations. As a result, these NSG-SGM3 mice allow superior engraftment of diverse hematopoietic lineages and primary AML samples than other models and are useful for immuno-oncology, immunology and infectious disease studies.

Donating Investigator

James C Mulloy, Cincinnati Children's Hospital Medical Center

Genetic overview

Genetic Background	Generation
	N12+N1F4pF3p (17-NOV-15)

Il2rg^tm1Wjl

Allele Type	Gene Symbol	Gene Name
Targeted (Null/Knockout)	Il2rg	interleukin 2 receptor, gamma chain

Prkdc^scid

Allele Type	Gene Symbol	Gene Name
Spontaneous	Prkdc	protein kinase, DNA activated, catalytic polypeptide

Tg(CMV-IL3,CSF2,KITLG)1Eav

Allele Type
Transgenic (Humanized sequence, Inserted expressed sequence)

View Genetics

Research Applications

Cancer Research
Immunology, Inflammation and Autoimmunity Research
Internal/Organ Research
Research Tools
Virology Research

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Base Price

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$245.00 Domestic price for male 3-week

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Details

Detailed Description

These mice contain three coinjected transgenes, human interleukin-3 (IL-3), human granulocyte/macrophage-stimulating factor (GM-CSF), and human Steel factor (SF) gene, each driven by a human cytomegalovirus promoter/enhancer sequence. These mice are maintained on the NOD.Cg-Prkdc^scid Il2rg^tm1Wjl/SzJ mice (Stock No. 005557) background. These mice constitutively produce 2-4 ng/ml serum levels of human IL-3, GM-CSF, and SF. The Il2rg-/- specific NOD.SCID background supports human and murine hematopoietic cell engraftment, and suppresses human erythropoiesis, enhances human myelopoiesis, and reduces human B-lymphopoiesis in mice after transplant of bone marrow or liver cells.

View Flow Cytometry Characterization Data for Immunodeficient JAX Strains

Development

Three separate transgenes were designed each carrying either the human interleukin-3 (IL-3) gene, the human granulocyte/macrophage-stimulating factor (GM-CSF) gene, or human Steel factor (SF) gene. Expression of each gene is driven by a human cytomegalovirus promoter/enhancer sequence, and is followed by a human growth hormone cassette and a polyadenylation (polyA) sequence. The transgenes were microinjected into fertilized C57BL/6xC3H/HeN oocytes. The resulting founders, carrying all three transgenes (3GS) were backcrossed to BALB/c-scid/scid mice for several generations and subsequently backcrossed to NOD.CB17-Prkdc^scid mice for at least 11 generations. These mice were bred to NOD.Cg-Prkdc^scid Il2rg^tm1Wjl mice, and were then interbred until all offspring were homozygous for 3GS and the IL2rg targeted mutation. Upon arrival at The Jackson Laboratory, transgenic mice were bred to NOD.Cg-Prkdc^scid Il2rg^tm1Wjl/SzJ mice (Stock No. 005557) for one generation to establish the colony. Thereafter, females homozygous for Prkdc^scid, homozygous for Il2rg^tm1Wjl and homozygous for the 3GS transgenes were bred with males homozygous for Prkdc^scid, hemizygous for the X-linked Il2rg^tm1Wjl and homozygous for the 3GS transgenes.

Expression Data

Expressed Gene	CSF2, colony stimulating factor 2, human
Expressed Gene	IL3, interleukin 3, human
Expressed Gene	KITLG, KIT ligand, human
Site of Expression

Control Suggestions

Additional Information

Considerations for Choosing Controls

Selected References

Billerbeck E; Barry WT; Mu K; Dorner M; Rice CM; Ploss A. 2011. Development of human CD4+FoxP3+ regulatory T cells in human stem cell factor-, granulocyte-macrophage colony-stimulating factor-, and interleukin-3-expressing NOD-SCID IL2R{gamma}null humanized mice. Blood 117(11):3076-86. PubMed: 21252091 MGI: J:170510
Bryce PJ; Falahati R; Kenney LL; Leung J; Bebbington C; Tomasevic N; Krier RA; Hsu CL; Shultz LD; Greiner DL; Brehm MA. 2016. Humanized mouse model of mast cell-mediated passive cutaneous anaphylaxis and passive systemic anaphylaxis. J Allergy Clin Immunol :. PubMed: 27139822 MGI: J:231799
Coughlan AM; Harmon C; Whelan S; O'Brien EC; O'Reilly VP; Crotty P; Kelly P; Ryan M; Hickey FB; O'Farrelly C; Little MA. 2016. Myeloid Engraftment in Humanized Mice: Impact of Granulocyte-Colony Stimulating Factor Treatment and Transgenic Mouse Strain. Stem Cells Dev 25(7):530-41. PubMed: 26879149 MGI: J:230785
Wunderlich M; Chou FS; Link KA; Mizukawa B; Perry RL; Carroll M; Mulloy JC. 2010. AML xenograft efficiency is significantly improved in NOD/SCID-IL2RG mice constitutively expressing human SCF, GM-CSF and IL-3. Leukemia 24(10):1785-8. PubMed: 20686503 MGI: J:166359

View All References

Genetics

Il2rg^tm1Wjl

Allele Symbol: Il2rg^tm1Wjl

Allele Name	targeted mutation 1, Warren J Leonard
Allele Type	Targeted (Null/Knockout)
Allele Synonym(s)	CD132^-; IL2Rgamma^null; Il2rg^tm1Wjll; [KO]gammac; gammac^-; gc^-
Gene Symbol and Name	Il2rg, interleukin 2 receptor, gamma chain
Gene Synonym(s)	Ab2-183; CD132; CIDX; Cd132; IL-2RG; IMD4; P64; SCIDX; SCIDX1; [g]c; common cytokine receptor gamma chain; common gamma chain; gamma C receptor; gamma(c); gammaC; gc
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

Prkdc^scid

Allele Symbol: Prkdc^scid

Allele Name	severe combined immunodeficiency
Allele Type	Spontaneous
Allele Synonym(s)	SCID; scid
Gene Symbol and Name	Prkdc, protein kinase, DNA activated, catalytic polypeptide
Gene Synonym(s)	AI326420; AU019811; DNA-PK; DNA-PKcs; DNAPDcs; DNAPK; DNPK1; DOXNPH; HYRC; HYRC1; IMD26; XRCC7; doxorubicin nephropathy; dxnph; dxnph; expressed sequence AI326420; expressed sequence AU019811; p350; scid; severe combined immunodeficiency; slip
Site of Expression	T and B lymphocytes.
Strain of Origin	C.B-17
Chromosome	16
Molecular Note	A T-to-A transversion point mutation at a position corresponding to codon 4095 created a premature stop codon.

Tg(CMV-IL3,CSF2,KITLG)1Eav

Allele Symbol: Tg(CMV-IL3,CSF2,KITLG)1Eav

Allele Name	transgene insertion 1, CJ Eaves
Allele Type	Transgenic (Humanized sequence, Inserted expressed sequence)
Allele Synonym(s)	3/GM/SF; SGM3; Tg(hSCF/hGM-CSF/hIL3
Gene Symbol and Name	Tg(CMV-IL3,CSF2,KITLG)1Eav, transgene insertion 1, CJ Eaves
Gene Synonym(s)	3/GM/SF
Promoter	CMV, cytomegalovirus, human
Expressed Gene	CSF2, colony stimulating factor 2, human
Expressed Gene	IL3, interleukin 3, human
Expressed Gene	KITLG, KIT ligand, human
Strain of Origin	(C57BL/6 x C3H/HeN)F1
Chromosome	UN
Molecular Note	cDNAs encoding human interleukin 3, colony stimulating factor 2 (granulocyte-macrophage) and kit ligand were independently ligated into expression cassettes in which the cDNA resides downstream of the cytomegalovirus (CMV) promoter/enhancer sequence and is followed by human growth factor intronic and polyadenylation sequences. A transgenic mouse that was shown by ELISA to have serum levels of all three growth factors at ng/ml levels was used to establish a line with the same phenotype.

Disease/Phenotype

Disease Terms

Research Areas By Genotype

This mouse can be used to support research in many areas including:

Genotype: Il2rg^tm1Wjl related

Cancer Research
- Growth Factors/Receptors/Cytokines
Immunology, Inflammation and Autoimmunity Research
- Growth Factors/Receptors/Cytokines

Genotype: Prkdc^scid related

Immunology, Inflammation and Autoimmunity Research
- Immunodeficiency
  - B and T cell deficiency
Internal/Organ Research
- Lymphoid Tissue Defects
  - B and T cell deficiency
Research Tools
- Cancer Research
  - B and T cell deficiency, xenograft/transplant host
- Toxicology Research
  - xenograft/transplant host
Virology Research
- B and T Cell Deficiency
  - AIDS research tool

Phenotype Information

Body Weight Information - JAX® Mice Strain - NOD.Cg-Prkdc^scidIl2rg^tm1WjlTg(CMV-IL3,CSF2,KITLG)1Eav/MloySzJ

References

Billerbeck E; Barry WT; Mu K; Dorner M; Rice CM; Ploss A. 2011. Development of human CD4+FoxP3+ regulatory T cells in human stem cell factor-, granulocyte-macrophage colony-stimulating factor-, and interleukin-3-expressing NOD-SCID IL2R{gamma}null humanized mice. Blood 117(11):3076-86. PubMed: 21252091 MGI: J:170510
Bryce PJ; Falahati R; Kenney LL; Leung J; Bebbington C; Tomasevic N; Krier RA; Hsu CL; Shultz LD; Greiner DL; Brehm MA. 2016. Humanized mouse model of mast cell-mediated passive cutaneous anaphylaxis and passive systemic anaphylaxis. J Allergy Clin Immunol :. PubMed: 27139822 MGI: J:231799
Coughlan AM; Harmon C; Whelan S; O'Brien EC; O'Reilly VP; Crotty P; Kelly P; Ryan M; Hickey FB; O'Farrelly C; Little MA. 2016. Myeloid Engraftment in Humanized Mice: Impact of Granulocyte-Colony Stimulating Factor Treatment and Transgenic Mouse Strain. Stem Cells Dev 25(7):530-41. PubMed: 26879149 MGI: J:230785
Wunderlich M; Chou FS; Link KA; Mizukawa B; Perry RL; Carroll M; Mulloy JC. 2010. AML xenograft efficiency is significantly improved in NOD/SCID-IL2RG mice constitutively expressing human SCF, GM-CSF and IL-3. Leukemia 24(10):1785-8. PubMed: 20686503 MGI: J:166359

Additional - Il2rg^tm1Wjl related

Accardi R; Gruffat H; Sirand C; Fusil F; Gheit T; Hernandez-Vargas H; Le Calvez-Kelm F; Traverse-Glehen A; Cosset FL; Manet E; Wild CP; Tommasino M. 2015. The mycotoxin aflatoxin B1 stimulates Epstein-Barr virus-induced B-cell transformation in in vitro and in vivo experimental models. Carcinogenesis 36(11):1440-51. PubMed: 26424750 MGI: J:226625
Agliano A; Martin-Padura I; Mancuso P; Marighetti P; Rabascio C; Pruneri G; Shultz LD; Bertolini F. 2008. Human acute leukemia cells injected in NOD/LtSz-scid/IL-2Rgamma null mice generate a faster and more efficient disease compared to other NOD/scid-related strains. Int J Cancer 123(9):2222-7. PubMed: 18688847 MGI: J:142410
Akkina R; Berges BK; Palmer BE; Remling L; Neff CP; Kuruvilla J; Connick E; Folkvord J; Gagliardi K; Kassu A; Akkina SR. 2011. Humanized Rag1gammac Mice Support Multilineage Hematopoiesis and Are Susceptible to HIV-1 Infection via Systemic and Vaginal Routes. PLoS One 6(6):e20169. PubMed: 21695116 MGI: J:174292
Al-Shami A; Spolski R; Kelly J; Fry T; Schwartzberg PL; Pandey A; Mackall CL; Leonard WJ. 2004. A role for thymic stromal lymphopoietin in CD4(+) T cell development. J Exp Med 200(2):159-68. PubMed: 15263024 MGI: J:108209
Ali N; Flutter B; Sanchez Rodriguez R; Sharif-Paghaleh E; Barber LD; Lombardi G; Nestle FO. 2012. Xenogeneic graft-versus-host-disease in NOD-scid IL-2Rgammanull mice display a T-effector memory phenotype. PLoS One 7(8):e44219. PubMed: 22937164 MGI: J:191672
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van den Pol AN. 2009. Brain trauma enhances transient cytomegalovirus invasion of the brain only in mice that are immunodeficient. J Virol 83(1):420-7. PubMed: 18945784 MGI: J:153392
van der Touw W; Cravedi P; Kwan WH; Paz-Artal E; Merad M; Heeger PS. 2013. Cutting edge: Receptors for C3a and C5a modulate stability of alloantigen-reactive induced regulatory T cells. J Immunol 190(12):5921-5. PubMed: 23690475 MGI: J:204834
von Herrath MG; Dockter J; Oldstone MB. 1994. How virus induces a rapid or slow onset insulin-dependent diabetes mellitus in a transgenic model. Immunity 1(3):231-42. PubMed: 7889411 MGI: J:81287

Additional - Tg(CMV-IL3,CSF2,KITLG)1Eav related

Bruedigam C; Bagger FO; Heidel FH; Paine Kuhn C; Guignes S; Song A; Austin R; Vu T; Lee E; Riyat S; Moore AS; Lock RB; Bullinger L; Hill GR; Armstrong SA; Williams DA; Lane SW. 2014. Telomerase inhibition effectively targets mouse and human AML stem cells and delays relapse following chemotherapy. Cell Stem Cell 15(6):775-90. PubMed: 25479751 MGI: J:223853
Nicolini FE; Cashman JD; Hogge DE; Humphries RK; Eaves CJ. 2004. NOD/SCID mice engineered to express human IL-3, GM-CSF and Steel factor constitutively mobilize engrafted human progenitors and compromise human stem cell regeneration. Leukemia 18(2):341-7. PubMed: 14628073 MGI: J:87755
Wei J; Wunderlich M; Fox C; Alvarez S; Cigudosa JC; Wilhelm JS; Zheng Y; Cancelas JA; Gu Y; Jansen M; Dimartino JF; Mulloy JC. 2008. Microenvironment determines lineage fate in a human model of MLL-AF9 leukemia. Cancer Cell 13(6):483-95. PubMed: 18538732 MGI: J:166360
Wunderlich M; Brooks RA; Panchal R; Rhyasen GW; Danet-Desnoyers G; Mulloy JC. 2014. OKT3 prevents xenogeneic GVHD and allows reliable xenograft initiation from unfractionated human hematopoietic tissues. Blood 123(24):e134-44. PubMed: 24778156 MGI: J:217446

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QUANTITY	VOLUME PRICING
Volume pricing is not available for International Commercial & For-Profit.

Also Known As: NOD-scid IL2Rgnull-3/GM/SF, NSG-SGM3, NSGS

Donating Investigator

Genetic overview

Research Applications

Base Price

Volume Pricing Available!

Detailed Description

Development

Expression Data

Control Suggestions

Additional Information

Selected References

Il2rgtm1Wjl

Allele Symbol: Il2rgtm1Wjl

Prkdcscid

Allele Symbol: Prkdcscid

Tg(CMV-IL3,CSF2,KITLG)1Eav

Allele Symbol: Tg(CMV-IL3,CSF2,KITLG)1Eav

Disease Terms

Research Areas By Genotype

This mouse can be used to support research in many areas including:

Genotype: Il2rgtm1Wjl related

Genotype: Prkdcscid related

Phenotype Information

References

Additional - Il2rgtm1Wjl related

Additional - Prkdcscid related

Additional - Tg(CMV-IL3,CSF2,KITLG)1Eav related

Genotyping Protocols

Dietary Information

Breeding Considerations

Mating System

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Animal Health Reports

Live Mouse

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Il2rg^tm1Wjl

Allele Symbol: Il2rg^tm1Wjl

Prkdc^scid

Allele Symbol: Prkdc^scid

Genotype: Il2rg^tm1Wjl related

Genotype: Prkdc^scid related

Additional - Il2rg^tm1Wjl related

Additional - Prkdc^scid related