Strain Name:

C;129S4-Rag2tm1.1Flv Csf1tm1.1(CSF1)Flv Il2rgtm1.1Flv/J

Stock Number:

017708

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Availability:

Under Development - Now Accepting Orders

Estimated Available for Distribution Date: 15-SEP-14
Use Restrictions Apply, see Terms of Use
These humanized immunodeficient mice express human mCSF (CSF1) on a Rag2/Il2rg deficient background, significantly increasing their ability to engraft and maintain human hematopoietic cells.

Description

Strain Information

Former Names C;129S4-Rag2tm1.1Flv Csf1tm1.1(CSF1)Vlcg Il2rgtm1.1Flv/J    (Changed: 08-APR-14 )
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)   20-APR-12
Specieslaboratory mouse
 
Donating InvestigatorDr. Richard A. Flavell,   Yale University School of Medicine

Description
Csf1 (colony stimulating factor 1 (macrophage)) is a cytokine that plays several physiological roles, among them the promotion of myeloid cell differentiation. CSF1 is believed to interact with hematopoietic stem cells to regulate the maturation, survival, adhesion and motility of macrophages.

Human mCSF (CSF1) replaces expression of mouse Csf1 in these Rag2/Il2rg knockout mice lacking T, B, and NK cells (see Stock No. 014593). Animals faithfully express a functional human CSF1 protein that is recognized by the mouse system both qualitatively and quantitatively. Unlike Csf1op homozygous mice (Stock No. 000231), these animals exhibit normal teeth and bone properties as well as normal bone marrow cell content, myeloid cell frequencies in the bone marrow, spleen, and peripheral blood, and macrophage frequencies in the bone marrow and spleen.

Human CSF1 significantly increases the ability of the mice to engraft and maintain human hematopoietic cells. Intra-hepatic transfer of human fetal liver-derived hematopoietic stem and progenitor cells (CD34+) to newborn mice results in more efficient differentiation and enhanced frequencies of human monocytes/macrophages in bone marrow, spleen, peripheral blood, lungs, liver and the peritoneal cavity. Significant proportions of human CD14+CD33+ cells are observed at 16-20 weeks.

Development
Exons 2-9 of the human mCSF (CSF1) gene and a loxP-flanked neomycin cassette were knocked into intron 2 of the mouse Csf1 locus, replacing the endogenous gene. The promoter and other regulatory elements (including the 5' UTR) of the mouse gene were preserved in the targeting vector. An embryonic stem (ES) cell line carrying deletions in the Rag2 and Il2rg genes was used to create the mutation (* below). Correctly targeted ES cells were electroporated with a Cre-expressing vector to remove the drug selection cassette. This strain was maintained on a mixed BALB/c-129 genetic background by the donating laboratory.

*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.

Control Information

  Control
   None Available
 
  Considerations for Choosing Controls

Related Strains

View Strains carrying   Csf1tm1.1(CSF1)Flv     (2 strains)

View Strains carrying   Il2rgtm1.1Flv     (6 strains)

View Strains carrying   Rag2tm1.1Flv     (6 strains)

Strains carrying other alleles of Csf1
000231   B6;C3Fe a/a-Csf1op/J
View Strains carrying other alleles of Csf1     (1 strain)

View Strains carrying other alleles of Il2rg     (20 strains)

View Strains carrying other alleles of Rag2     (6 strains)

Phenotype

Phenotype Information

View Related Disease (OMIM) Terms

View Mammalian Phenotype Terms

Mammalian Phenotype Terms provided by MGI
      assigned by genotype

Csf1tm1.1(CSF1)Flv/Csf1tm1.1(CSF1)Flv Il2rgtm1.1Flv/Il2rgtm1.1Flv Rag2tm1.1Flv/Rag2tm1.1Flv

        involves: 129P2/OlaHsd * 129S/SvEv * 129S4/SvJae * BALB/cAnNTac
  • immune system phenotype
  • *normal* immune system phenotype
    • mice exhibit normal total cell content of the bone marrow, frequencies of myeloid cells in the bone marrow, spleen, and peripheral blood, and the frequencies of macrophages in the bone marrow and spleen   (MGI Ref ID J:177073)
    • abnormal immune system physiology
      • mice produce humanized monocytes/macrophages with augmented functional properties (migration, phagocytosis, activation, and responses to LPS) and production of human cytokines   (MGI Ref ID J:177073)
  • skeleton phenotype
  • *normal* skeleton phenotype
    • mice exhibit normal bones   (MGI Ref ID J:177073)
  • craniofacial phenotype
  • *normal* craniofacial phenotype
    • mice exhibit normal teeth   (MGI Ref ID J:177073)
  • hematopoietic system phenotype
  • *normal* hematopoietic system phenotype
    • mice exhibit normal total cell content of the bone marrow, frequencies of myeloid cells in the bone marrow, spleen, and peripheral blood, and the frequencies of macrophages in the bone marrow and spleen   (MGI Ref ID J:177073)
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
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 Csf1tm1.1(CSF1)Flv
Allele Name targeted mutation 1.1, Richard A Flavell
Allele Type Targeted (knock-in)
Common Name(s) CSF1h; Csf1tm1.1(CSF1)Vlcg;
Strain of Origin(BALB/cJ x 129S4/SvJae)F1
Expressed Gene CSF1, colony stimulating factor 1 (macrophage), human
General Note This allele was originally generated in v17.2 ES cells homozygous for Il2rgtm1Cgn and Rag2tm1Fwa.
Molecular Note The mouse open reading frame (exon 2 through 9) was replaced with the human gene from BAC RPCI-11, clone 101M23. A floxed neo cassette inserted downstream of the human sequence was removed by cre-mediated recombination. [MGI Ref ID J:177073]
 
Gene Symbol and Name Csf1, colony stimulating factor 1 (macrophage)
Chromosome 3
Gene Common Name(s) C87615; CSF-1; Csfm; M-CSF; MCSF; colony stimulating factor, macrophage; colony-stimulating factor-1; expressed sequence C87615; op; osteopetrosis;
 
Allele Symbol Il2rgtm1.1Flv
Allele Name targeted mutation 1.1, Richard A Flavell
Allele Type Targeted (knock-out)
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 (knock-out)
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

Csf1tm1.1(CSF1)Vlcg, Separated PCR
Il2rgtm1.1Flv, Standard PCR
Rag2tm1.1Flv, Standard PCR


Helpful Links

Genotyping resources and troubleshooting

References

References provided by MGI

Selected Reference(s)

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]

Additional References

Csf1tm1.1(CSF1)Flv related

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]

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]

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]

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]

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]

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]

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]

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]

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]

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

Colony Maintenance

Breeding & HusbandryRag2-/- Csf1-/- Il2rg-/- females and Rag2-/- Csf1-/- Il2rg-/0 males may be bred, but are considered to be relatively poor breeders. Prophylactic antibiotic treatment may be considered for this immunodeficient colony. Il2rg is an X-linked gene.
Mating SystemSee Colony Maintenance under the Health & Care tab         (Female x Male)   20-APR-12

Pricing and Purchasing

Pricing, Supply Level & Notes, Controls


 

This strain is currently Under Development - Now Accepting Orders.
Estimated Available for Distribution Date: 15-SEP-14

Please note: You may now place orders for this strain although it is not yet ready for distribution. Estimated available for distribution dates are provided to keep customers better informed on strains under development. Please note that our Colony Managers routinely monitor the target date and edit it based on breeding performance and other factors. The length of time it takes to make a new strain available for distribution depends on genotype, age, number of animals sent by the Donating Investigator, breeding performance, additional strain development (backcrossing, making homozygous), and anticipated demand for the strain.

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

Live Mice

Price per mouse (US dollars $)GenderGenotypes Provided
Individual Mouse $232.00MaleHomozygous for Rag2tm1.1Flv, Homozygous for Csf1tm1.1(CSF1)Flv, Hemizygous for Il2rgtm1.1Flv  
$232.00FemaleHomozygous for Rag2tm1.1Flv, Homozygous for Csf1tm1.1(CSF1)Flv, Homozygous for Il2rgtm1.1Flv  
Price per Pair (US dollars $)Pair Genotype
$464.00Homozygous for Rag2tm1.1Flv, Homozygous for Csf1tm1.1(CSF1)Vlcg, Homozygous for Il2rgtm1.1Flv x Homozygous for Rag2tm1.1Flv, Homozygous for Csf1tm1.1(CSF1)Vlcg, Hemizygous for Il2rgtm1.1Flv  

Standard Supply

Under Development - Now Accepting Orders The strain development process (i.e. importation, rederivation, and colony expansion) usually takes six to nine months.

Pricing for International shipping destinations View USA Canada and Mexico Pricing

Live Mice

Price per mouse (US dollars $)GenderGenotypes Provided
Individual Mouse $301.60MaleHomozygous for Rag2tm1.1Flv, Homozygous for Csf1tm1.1(CSF1)Flv, Hemizygous for Il2rgtm1.1Flv  
$301.60FemaleHomozygous for Rag2tm1.1Flv, Homozygous for Csf1tm1.1(CSF1)Flv, Homozygous for Il2rgtm1.1Flv  
Price per Pair (US dollars $)Pair Genotype
$603.20Homozygous for Rag2tm1.1Flv, Homozygous for Csf1tm1.1(CSF1)Vlcg, Homozygous for Il2rgtm1.1Flv x Homozygous for Rag2tm1.1Flv, Homozygous for Csf1tm1.1(CSF1)Vlcg, Hemizygous for Il2rgtm1.1Flv  

Standard Supply

Under Development - Now Accepting Orders The strain development process (i.e. importation, rederivation, and colony expansion) usually takes six to nine months.

View USA Canada and Mexico Pricing View International Pricing

Standard Supply

Under Development - Now Accepting Orders The strain development process (i.e. importation, rederivation, and colony expansion) usually takes six to nine months.

Control Information

  Control
   None Available
 
  Considerations for Choosing Controls
  Control Pricing Information for Genetically Engineered Mutant Strains.
 

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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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