Strain Name:

C;129S4-Rag2tm1.1Flv Il2rgtm1.1Flv/J

Stock Number:

014593

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Availability:

Repository- Live

Use Restrictions Apply, see Terms of Use
These Rag2/Il2rg compound mutant mice (also called Rag2-/- γc-/- mice) exhibit T cell, B cell and NK cell immunodeficiencies that make them effective transplant hosts for human immune cells.

Description

Strain Information

Former Names C;129S4-Rag2tm1Flv Il2rgtm1Flv/J    (Changed: 14-FEB-11 )
Type Mutant Stock; Targeted Mutation;
Additional information on Genetically Engineered and Mutant Mice.
Visit our online Nomenclature tutorial.
Mating SystemSee Colony Maintenance under the Health & Care tab         (Female x Male)   17-MAY-11
Specieslaboratory mouse
GenerationF?+F6 (27-DEC-13)
Generation Definitions
 
Donating InvestigatorDr. Richard A. Flavell,   Yale University School of Medicine

Description
Both the Rag2 and the X-linked Il2rg genes were targeted in these compound mutant mice. Homozygous Rag2 and hemizygous male/homozygous female Il2rg animals lack T, B, and NK cells. Their immunodeficiencies make them particularly useful as transplant hosts. Human fetal liver hematopoietic stem and progenitor cell transplants create a humanized model that may be used to develop and test novel immune therapeutic and preventative strategies.

The creation of this strain was funded by the Bill and Melinda Gates Foundation.

Development
V17 embryonic stem (ES) cells (derived from BALB/cTac x 129S4/SvJae mice) were used to sequentially delete the coding regions of the Rag2 and X chromosome-linked Il2rg genes. A loxP-flanked PGK-neomycin cassette was targeted to Rag2 and a loxP-flanked human ubiquitin promoter-driven hygromycin cassette was directed to Il2rg. Transient infection with a cre plasmid excised the floxed segments. Chimeras were crossed once to BALB/c and the mice were intercrossed to produce mice that are homozygous for the Rag2 mutation and hemizygous/homozygous for the Il2rg mutation.

Related Strains

View Strains carrying   Il2rgtm1.1Flv     (6 strains)

View Strains carrying   Rag2tm1.1Flv     (6 strains)

View Strains carrying other alleles of Il2rg     (22 strains)

Strains carrying other alleles of Rag2
008449   B6(Cg)-Rag2tm1.1Cgn/J
007790   B6;129P2-Rag1/Rag2tm1Mnz/J
008448   C.B6(Cg)-Rag2tm1.1Cgn/J
008309   C57BL/6-Rag2tm1Cgn/J
008338   CByJ.B6(Cg)-Rag2tm1Cgn/J
View Strains carrying other alleles of Rag2     (5 strains)

Phenotype

Phenotype Information

View Related Disease (OMIM) Terms

View Mammalian Phenotype Terms

Mammalian Phenotype Terms provided by MGI
      assigned by genotype

Il2rgtm1.1Flv/Il2rgtm1.1Flv Rag2tm1.1Flv/Rag2tm1.1Flv

        involves: 129S4/SvJae * BALB/cAnNTac
  • immune system phenotype
  • abnormal response to transplant
    • mice exhibit engraftment with human fetal liver hematopoietic and progenitor cells to reconstitution a functional human immune system   (MGI Ref ID J:168303)
  • increased susceptibility to bacterial infection
    • mice engrafted with human fetal liver hematopoietic and progenitor cells support S. Typhi replication and persistent infection   (MGI Ref ID J:168303)

Il2rgtm1.1Flv/Y Rag2tm1.1Flv/Rag2tm1.1Flv

        involves: 129S4/SvJae * BALB/cAnNTac
  • immune system phenotype
  • abnormal response to transplant
    • mice exhibit engraftment with human fetal liver hematopoietic and progenitor cells to reconstitution a functional human immune system   (MGI Ref ID J:168303)
  • increased susceptibility to bacterial infection
    • mice engrafted with human fetal liver hematopoietic and progenitor cells support S. Typhi replication and persistent infection   (MGI Ref ID J:168303)
View Research Applications

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

Immunology, Inflammation and Autoimmunity Research
Immunodeficiency
      B and T cell deficiency
      B cell deficiency
      B, T, and NK cell deficiency
      NK Cell Deficiency
      T cell deficiency

Research Tools
Hematological Research
Immunology, Inflammation and Autoimmunity Research
      B, T, and NK cell deficiency
      T cell deficiency, xenograft/transplant host

Genes & Alleles

Gene & Allele Information provided by MGI

 
Allele Symbol Il2rgtm1.1Flv
Allele Name targeted mutation 1.1, Richard A Flavell
Allele Type Targeted (Null/Knockout)
Strain of OriginBALB/cAnNTac x 129S4/SvJae
Gene Symbol and Name Il2rg, interleukin 2 receptor, gamma chain
Chromosome X
Gene Common Name(s) CD132; CIDX; IL-2RG; IMD4; P64; SCIDX; SCIDX1; [g]c; common cytokine receptor gamma chain; common gamma chain; gamma C receptor; gamma(c); gc;
General Note Originally generated in conjunction with Rag2tm1.1Flv.
Molecular Note A floxed human ubiquitin promoter-driven hygromycin cassette replaced the coding region. Cre-mediated recombination removed the hygro cassette. [MGI Ref ID J:168303]
 
Allele Symbol Rag2tm1.1Flv
Allele Name targeted mutation 1.1, Richard A Flavell
Allele Type Targeted (Null/Knockout)
Strain of OriginBALB/cAnNTac x 129S4/SvJae
Gene Symbol and Name Rag2, recombination activating gene 2
Chromosome 2
Gene Common Name(s) RAG-2; Rag-2;
General Note Originally generated in conjunction with Il2rgtm1.1Flv.
Molecular Note A floxed PGK-neomycin cassette replaced the coding region. Cre-mediated recombination removed the neo cassette. [MGI Ref ID J:168303]

Genotyping

Genotyping Information

Genotyping Protocols

Il2rgtm1.1Flv, Standard PCR
Rag2tm1.1Flv, Standard PCR
Generic Hygromycin, QPCR


Helpful Links

Genotyping resources and troubleshooting

References

References provided by MGI

Selected Reference(s)

Song J; Willinger T; Rongvaux A; Eynon EE; Stevens S; Manz MG; Flavell RA; Galan JE. 2010. A mouse model for the human pathogen Salmonella typhi. Cell Host Microbe 8(4):369-76. [PubMed: 20951970]  [MGI Ref ID J:168303]

Additional References

Il2rgtm1.1Flv related

Keppel MP; Yang L; Cooper MA. 2013. Murine NK Cell Intrinsic Cytokine-Induced Memory-like Responses Are Maintained following Homeostatic Proliferation. J Immunol 190(9):4754-62. [PubMed: 23530145]  [MGI Ref ID J:195522]

Muller AJ; Filipe-Santos O; Eberl G; Aebischer T; Spath GF; Bousso P. 2012. CD4+ T cells rely on a cytokine gradient to control intracellular pathogens beyond sites of antigen presentation. Immunity 37(1):147-57. [PubMed: 22727490]  [MGI Ref ID J:187413]

Pantelyushin S; Haak S; Ingold B; Kulig P; Heppner FL; Navarini AA; Becher B. 2012. Rorgammat+ innate lymphocytes and gammadelta T cells initiate psoriasiform plaque formation in mice. J Clin Invest 122(6):2252-6. [PubMed: 22546855]  [MGI Ref ID J:188299]

Rankin LC; Groom JR; Chopin M; Herold MJ; Walker JA; Mielke LA; McKenzie AN; Carotta S; Nutt SL; Belz GT. 2013. The transcription factor T-bet is essential for the development of NKp46(+) innate lymphocytes via the Notch pathway. Nat Immunol 14(4):389-95. [PubMed: 23455676]  [MGI Ref ID J:194819]

Rathinam C; Poueymirou WT; Rojas J; Murphy AJ; Valenzuela DM; Yancopoulos GD; Rongvaux A; Eynon EE; Manz MG; Flavell RA. 2011. Efficient differentiation and function of human macrophages in humanized CSF-1 mice. Blood 118(11):3119-28. [PubMed: 21791433]  [MGI Ref ID J:177073]

Rongvaux A; Willinger T; Martinek J; Strowig T; Gearty SV; Teichmann LL; Saito Y; Marches F; Halene S; Palucka AK; Manz MG; Flavell RA. 2014. Development and function of human innate immune cells in a humanized mouse model. Nat Biotechnol :. [PubMed: 24633240]  [MGI Ref ID J:207289]

Rongvaux A; Willinger T; Takizawa H; Rathinam C; Auerbach W; Murphy AJ; Valenzuela DM; Yancopoulos GD; Eynon EE; Stevens S; Manz MG; Flavell RA. 2011. Human thrombopoietin knockin mice efficiently support human hematopoiesis in vivo. Proc Natl Acad Sci U S A 108(6):2378-83. [PubMed: 21262827]  [MGI Ref ID J:168301]

Silva A; Laranjeira AB; Martins LR; Cardoso BA; Demengeot J; Yunes JA; Seddon B; Barata JT. 2011. IL-7 Contributes to the Progression of Human T-cell Acute Lymphoblastic Leukemias. Cancer Res 71(14):4780-9. [PubMed: 21593192]  [MGI Ref ID J:174087]

Strowig T; Rongvaux A; Rathinam C; Takizawa H; Borsotti C; Philbrick W; Eynon EE; Manz MG; Flavell RA. 2011. Transgenic expression of human signal regulatory protein alpha in Rag2-/-gamma(c)-/- mice improves engraftment of human hematopoietic cells in humanized mice. Proc Natl Acad Sci U S A 108(32):13218-23. [PubMed: 21788509]  [MGI Ref ID J:175623]

Taylor PR; Roy S; Leal SM Jr; Sun Y; Howell SJ; Cobb BA; Li X; Pearlman E. 2014. Activation of neutrophils by autocrine IL-17A-IL-17RC interactions during fungal infection is regulated by IL-6, IL-23, RORgammat and dectin-2. Nat Immunol 15(2):143-51. [PubMed: 24362892]  [MGI Ref ID J:209279]

Willinger T; Rongvaux A; Takizawa H; Yancopoulos GD; Valenzuela DM; Murphy AJ; Auerbach W; Eynon EE; Stevens S; Manz MG; Flavell RA. 2011. Human IL-3/GM-CSF knock-in mice support human alveolar macrophage development and human immune responses in the lung. Proc Natl Acad Sci U S A 108(6):2390-5. [PubMed: 21262803]  [MGI Ref ID J:168302]

Rag2tm1.1Flv related

Keppel MP; Yang L; Cooper MA. 2013. Murine NK Cell Intrinsic Cytokine-Induced Memory-like Responses Are Maintained following Homeostatic Proliferation. J Immunol 190(9):4754-62. [PubMed: 23530145]  [MGI Ref ID J:195522]

Martinez-Forero I; Azpilikueta A; Bolanos-Mateo E; Nistal-Villan E; Palazon A; Teijeira A; Perez-Chacon G; Morales-Kastresana A; Murillo O; Jure-Kunkel M; Zapata JM; Melero I. 2013. T cell costimulation with anti-CD137 monoclonal antibodies is mediated by K63-polyubiquitin-dependent signals from endosomes. J Immunol 190(12):6694-706. [PubMed: 23690480]  [MGI Ref ID J:204832]

Muller AJ; Filipe-Santos O; Eberl G; Aebischer T; Spath GF; Bousso P. 2012. CD4+ T cells rely on a cytokine gradient to control intracellular pathogens beyond sites of antigen presentation. Immunity 37(1):147-57. [PubMed: 22727490]  [MGI Ref ID J:187413]

Pantelyushin S; Haak S; Ingold B; Kulig P; Heppner FL; Navarini AA; Becher B. 2012. Rorgammat+ innate lymphocytes and gammadelta T cells initiate psoriasiform plaque formation in mice. J Clin Invest 122(6):2252-6. [PubMed: 22546855]  [MGI Ref ID J:188299]

Rankin LC; Groom JR; Chopin M; Herold MJ; Walker JA; Mielke LA; McKenzie AN; Carotta S; Nutt SL; Belz GT. 2013. The transcription factor T-bet is essential for the development of NKp46(+) innate lymphocytes via the Notch pathway. Nat Immunol 14(4):389-95. [PubMed: 23455676]  [MGI Ref ID J:194819]

Rathinam C; Poueymirou WT; Rojas J; Murphy AJ; Valenzuela DM; Yancopoulos GD; Rongvaux A; Eynon EE; Manz MG; Flavell RA. 2011. Efficient differentiation and function of human macrophages in humanized CSF-1 mice. Blood 118(11):3119-28. [PubMed: 21791433]  [MGI Ref ID J:177073]

Rongvaux A; Willinger T; Martinek J; Strowig T; Gearty SV; Teichmann LL; Saito Y; Marches F; Halene S; Palucka AK; Manz MG; Flavell RA. 2014. Development and function of human innate immune cells in a humanized mouse model. Nat Biotechnol :. [PubMed: 24633240]  [MGI Ref ID J:207289]

Rongvaux A; Willinger T; Takizawa H; Rathinam C; Auerbach W; Murphy AJ; Valenzuela DM; Yancopoulos GD; Eynon EE; Stevens S; Manz MG; Flavell RA. 2011. Human thrombopoietin knockin mice efficiently support human hematopoiesis in vivo. Proc Natl Acad Sci U S A 108(6):2378-83. [PubMed: 21262827]  [MGI Ref ID J:168301]

Silva A; Laranjeira AB; Martins LR; Cardoso BA; Demengeot J; Yunes JA; Seddon B; Barata JT. 2011. IL-7 Contributes to the Progression of Human T-cell Acute Lymphoblastic Leukemias. Cancer Res 71(14):4780-9. [PubMed: 21593192]  [MGI Ref ID J:174087]

Strowig T; Rongvaux A; Rathinam C; Takizawa H; Borsotti C; Philbrick W; Eynon EE; Manz MG; Flavell RA. 2011. Transgenic expression of human signal regulatory protein alpha in Rag2-/-gamma(c)-/- mice improves engraftment of human hematopoietic cells in humanized mice. Proc Natl Acad Sci U S A 108(32):13218-23. [PubMed: 21788509]  [MGI Ref ID J:175623]

Taylor PR; Roy S; Leal SM Jr; Sun Y; Howell SJ; Cobb BA; Li X; Pearlman E. 2014. Activation of neutrophils by autocrine IL-17A-IL-17RC interactions during fungal infection is regulated by IL-6, IL-23, RORgammat and dectin-2. Nat Immunol 15(2):143-51. [PubMed: 24362892]  [MGI Ref ID J:209279]

Willinger T; Rongvaux A; Takizawa H; Yancopoulos GD; Valenzuela DM; Murphy AJ; Auerbach W; Eynon EE; Stevens S; Manz MG; Flavell RA. 2011. Human IL-3/GM-CSF knock-in mice support human alveolar macrophage development and human immune responses in the lung. Proc Natl Acad Sci U S A 108(6):2390-5. [PubMed: 21262803]  [MGI Ref ID J:168302]

Health & husbandry

Health & Colony Maintenance Information

Animal Health Reports

Room Number           AX11

Colony Maintenance

Breeding & HusbandryWhen maintained as a live colony, mice that are both homozygous for the Rag2 mutation and hemizygous/homozygous for the X-linked Il2rg mutation may be intercrossed.
Mating SystemSee Colony Maintenance under the Health & Care tab         (Female x Male)   17-MAY-11
Diet Information LabDiet® 5K52/5K67

Pricing and Purchasing

Pricing, Supply Level & Notes, Controls


Pricing for USA, Canada and Mexico shipping destinations View International Pricing

Live Mice

Price per mouse (US dollars $)GenderGenotypes Provided
Individual Mouse $135.00MaleHomozygous for Rag2tm1.1Flv, Hemizygous for Il2rgtm1.1Flv  
$135.00FemaleHomozygous for Rag2tm1.1Flv, Homozygous for Il2rgtm1.1Flv  
Price per Pair (US dollars $)Pair Genotype
$270.00Homozygous for Rag2tm1.1Flv, Homozygous for Il2rgtm1.1Flv x Homozygous for Rag2tm1.1Flv, Hemizygous for Il2rgtm1.1Flv  

Standard Supply

Repository-Live.
Repository-Live represents an exclusive set of over 1800 unique mouse models across a vast array of research areas. Breeding colonies provide mice for large and small orders and fluctuate in size depending on current research demand. If a strain is not immediately available, you will receive an estimated availability timeframe for your inquiry or order in 2-3 business days. Repository strains typically are delivered at 4 to 8 weeks of age. Requests for specific ages will be noted but not guaranteed and we do not accept age requests for breeder pairs. However, if cohorts of mice (5 or more of one gender) are needed at a specific age range for experiments, we will do our best to accommodate your age request.

Pricing for International shipping destinations View USA Canada and Mexico Pricing

Live Mice

Price per mouse (US dollars $)GenderGenotypes Provided
Individual Mouse $175.50MaleHomozygous for Rag2tm1.1Flv, Hemizygous for Il2rgtm1.1Flv  
$175.50FemaleHomozygous for Rag2tm1.1Flv, Homozygous for Il2rgtm1.1Flv  
Price per Pair (US dollars $)Pair Genotype
$351.00Homozygous for Rag2tm1.1Flv, Homozygous for Il2rgtm1.1Flv x Homozygous for Rag2tm1.1Flv, Hemizygous for Il2rgtm1.1Flv  

Standard Supply

Repository-Live.
Repository-Live represents an exclusive set of over 1800 unique mouse models across a vast array of research areas. Breeding colonies provide mice for large and small orders and fluctuate in size depending on current research demand. If a strain is not immediately available, you will receive an estimated availability timeframe for your inquiry or order in 2-3 business days. Repository strains typically are delivered at 4 to 8 weeks of age. Requests for specific ages will be noted but not guaranteed and we do not accept age requests for breeder pairs. However, if cohorts of mice (5 or more of one gender) are needed at a specific age range for experiments, we will do our best to accommodate your age request.

View USA Canada and Mexico Pricing View International Pricing

Standard Supply

Repository-Live.
Repository-Live represents an exclusive set of over 1800 unique mouse models across a vast array of research areas. Breeding colonies provide mice for large and small orders and fluctuate in size depending on current research demand. If a strain is not immediately available, you will receive an estimated availability timeframe for your inquiry or order in 2-3 business days. Repository strains typically are delivered at 4 to 8 weeks of age. Requests for specific ages will be noted but not guaranteed and we do not accept age requests for breeder pairs. However, if cohorts of mice (5 or more of one gender) are needed at a specific age range for experiments, we will do our best to accommodate your age request.

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The Jackson Laboratory has rigorous genetic quality control and mutant gene genotyping programs to ensure the genetic background of JAX® Mice strains as well as the genotypes of strains with identified molecular mutations. JAX® Mice strains are only made available to researchers after meeting our standards. However, the phenotype of each strain may not be fully characterized and/or captured in the strain data sheets. Therefore, we cannot guarantee a strain's phenotype will meet all expectations. To ensure that JAX® Mice will meet the needs of individual research projects or when requesting a strain that is new to your research, we suggest ordering and performing tests on a small number of mice to determine suitability for your particular project.
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