Strain Name:

C;129S4-Rag2tm1.1Flv Csf1tm1.1(CSF1)Vlcg Csf2/Il3tm1.1(CSF2,IL3)Flv Thpotm1.1(TPO)Flv Il2rgtm1.1Flv/J

Stock Number:

017711

Availability:

Awaiting Transfer from the Donor

Use Restrictions Apply, see Terms of Use
Register Interest
Common Names: MITRG;    
MITRG are Rag2-deficient, Il2rg-deficient mice with human versions of three cytokines important for innate immune cell development (M-CSFh;IL-3/GM-CSFh;TPOh;Rag2-;γc-). MITRG mice are highly permissive for human hematopoiesis; supporting the development and function of monocytes, macrophages and NK cells derived from human fetal liver or adult CD34+ progenitor cells. MITRG is a humanized mouse for modelling the human immune system in scenarios of health and pathology, such as human cell engraftment and patient-derived tumor xenografts (PDX).

Description

Strain Information

Former Names C;129S4-Rag2tm1.1Flv Csf1tm1.1(CSF1)Vlcg Csf2/Il3tm1.1(CSF2,IL3)Flv Thpotm1.1(TPO)Flv 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.
Specieslaboratory mouse
 
Donating InvestigatorDr. Richard A. Flavell,   Yale University School of Medicine

Description
MITRG are Rag2-deficient, Il2rg-deficient mice with human versions of three cytokines important for innate immune cell development (M-CSFh;IL-3/GM-CSFh;TPOh;Rag2-;γc-). Because the human cytokines support the development and function of monocytes, macrophages and NK cells derived from human fetal liver or adult CD34+ progenitor cells injected into the mice, MITRG mice are highly permissive for human hematopoiesis and enable the full recapitulation of human myeloid development and function in the mouse. This humanized mouse model may be used to model the human immune system in scenarios of health and pathology, such as human cell engraftment and patient-derived tumor xenografts (PDX).

MITRG females homozygous for the five targeted mutations (i.e., MITRG homozygous females) are viable and fertile with a breeding lifespan of 6-8 months of age. MITRG males homozygous for the four somatic targeted mutations and hemizygous for the X-linked γc- mutation (i.e., MITRG homozygous males) are viable and fertile with a breeding lifespan of 6-8 months of age.

Development
MITRG mice harbor three humanized knock-in alleles (M-CSFh, IL-3/GM-CSFh and TPOh) and two knockout alleles (Rag2- and γc-), all designed by Dr. Richard A. Flavell (Yale University School of Medicine, HHMI).

The Rag2- (Rag2tm1.1Flv) and γc- (Il2rgtm1.1Flv) knockout alleles were created in (BALB/cAnNTac x 129S4/SvJae)-derived V17.2 embryonic stem (ES) cells. The recombination activating gene 2 (Rag2) coding region on chromosome 2 is replaced with a loxP-flanked PGK-neo cassette. The interleukin 2 receptor gamma chain (Il2rg) coding region on chromosome X is replaced with a loxP-flanked hUbp-hygro cassette. Correctly targeted ES cells were transiently transfected with a cre plasmid to delete the floxed cassettes. The resulting BALB/c;129 Rag2-;γc- ES cells were used for electroporation of the targeting vectors described below. Rag2-;γc- mice on a mixed BALB/c;129 genetic background are described and available from The Jackson Laboratory as Stock No. 014593.

The M-CSFh humanized knock-in allele (Csf1tm1.1(CSF1)Vlcg or CSF1h) replaces almost all the macrophage colony stimulating factor (Csf1) coding region on chromosome 11 with a 17.5 kbp human CSF1 sequence (exon 2 to 633nt downstream of noncoding exon 9) and a loxP-flanked hUbp-neo cassette. The Csf1 promoter and 5prime UTR are mouse origin. The targeting vector was electroporated into ES cells. Correctly re-targeted ES cells were transiently transfected with a cre plasmid to delete hUbp-Neo. Triple mutant mice (Rag2-;γc-;CSF1h) on a mixed BALB/c;129 genetic background are described and available from The Jackson Laboratory as Stock No. 017708.

The IL-3/GM-CSFh humanized knock-in allele (Csf2/Il3tm1.1(CSF2,IL3)Flv or hIL-3/GM-CSF) replaces the interleukin 3 (Il3) and granulocyte-macrophage colony stimulating factor (CSF2) coding regions on chromosome 11 with sequences encoding human IL3 and CSF2, and a loxP-flanked hUbp-neo cassette. The human IL3 knock-in is under control of mouse regulatory elements, while the human CSF2 knock-in is under control of its human regulatory elements. The targeting vector was electroporated into ES cells. Correctly re-targeted ES cells were transiently transfected with a cre plasmid to delete hUbp-Neo. Chimeric mice were bred with Balb/cAnNCr. Triple mutant mice (Rag2-;γc-;IL-3/GM-CSFh) on a mixed BALB/c;129 genetic background are described and available from The Jackson Laboratory as Stock No. 014595.

The TPOh humanized knock-in allele (Thpotm1.1(TPO)Flv) replaces the thrombopoietin (Thpo or Tpo) coding region on chromosome 16 with human THPO sequences and a loxP-flanked hUbp-neo cassette. The Thpo promoter and 5prime UTR are of mouse origin. The targeting vector was electroporated into ES cells. Correctly re-targeted ES cells were transiently transfected with a cre plasmid to delete hUbp-Neo. Triple mutant mice (Rag2-;γc-;TPOh) on a mixed BALB/c;129 genetic background are described and available from The Jackson Laboratory as Stock No. 014594.

To generate the MITRG mice, Dr. Flavell bred the three triple mutant mouse lines together. MITRG mice were maintained on a mixed BALB/c;129 genetic background prior to sending to The Jackson Laboratory in 2014 as Stock No. 017711.

Control Information

  Control
   See control note:

Depending upon the experiment, the following may be appropriate control strain(s):
--BALB/c;129 Rag2-;γc- (Stock No. 014593)
--BALB/c;129 Rag2-;γc-;TPOh (Stock No. 014594)
--BALB/c;129 Rag2-;γc-;IL-3/GM-CSFh (Stock No. 014595)
--BALB/c;129 Rag2-;γc-;CSF1h (Stock No. 017708)
--BALB/c;129 Rag2-;M-CSFh;IL-3/GM-CSFh;TPOh;γc-;hSIRPAtg (Stock No. 017712)

 
  Considerations for Choosing Controls

Related Strains

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

View Strains carrying   Csf2/Il3tm1.1(CSF2,IL3)Flv     (2 strains)

View Strains carrying   Il2rgtm1.1Flv     (6 strains)

View Strains carrying   Rag2tm1.1Flv     (6 strains)

View Strains carrying   Thpotm1.1(TPO)Flv     (2 strains)

View Strains carrying other alleles of CSF2     (3 strains)

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

Strains carrying other alleles of Csf2
003068   B6.NOD-(Csf2-D11Mit42) (D17Mit21-D17Mit10)/J
003065   B6.NOD-(Csf2-D11Mit42)/J
008056   NOD.L-(Csf2-D11Mit339)/McdfJ
008055   NOD.L-(D11Mit314-Csf2)/McdfJ
View Strains carrying other alleles of Csf2     (4 strains)

View Strains carrying other alleles of IL3     (3 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)

Strains carrying other alleles of TPO
026512   B6(Cg)-Tg(TPO-cre/ERT2)1139Tyj/J
View Strains carrying other alleles of TPO     (1 strain)

Phenotype

Phenotype Information

View Related Disease (OMIM) Terms

Related Disease (OMIM) Terms provided by MGI
- Potential model based on gene homology relationships. Phenotypic similarity to the human disease has not been tested.
Combined Cellular and Humoral Immune Defects with Granulomas; CCHIDG   (RAG2)
Combined Immunodeficiency, X-Linked; CIDX   (IL2RG)
Omenn Syndrome   (RAG2)
Severe Combined Immunodeficiency, Autosomal Recessive, T Cell-Negative, B Cell-Negative, Nk Cell-Positive   (RAG2)
Severe Combined Immunodeficiency, X-Linked; SCIDX1   (IL2RG)
Thrombocythemia 1; THCYT1   (THPO)
- Potential model based on transgenic expression of an ortholog of a human gene that is associated with this disease. Phenotypic similarity to the human disease has not been tested.
Thyroid Dyshormonogenesis 2A; TDH2A   (TPO)
View Research Applications

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

Cancer Research
Growth Factors/Receptors/Cytokines
Toxicology
      B and T cell deficiency, xenograft/transplant host
      xenograft/transplant host

Developmental Biology Research
Internal/Organ Defects
      Lymphoid Tissue Defects
      hematopoietic defects
Lymphoid Tissue Defects
      hematopoietic defects

Hematological Research
Hematopoietic Defects
Immunological Defects
      B and T cell deficiency

Immunology, Inflammation and Autoimmunity Research
Autoimmunity
      B and T cell deficiency
      B cell deficiency
Graft vs. Host Disease
Growth Factors/Receptors/Cytokines
Immunodeficiency
      B and T cell deficiency
      B cell defects
      B cell deficiency
      B, T, and NK cell deficiency
      NK Cell Deficiency
      NK Cell and Cd8 T Cell defects
      T cell deficiency
      specific T cell deficiency
Inflammation
      B and T cell deficiency
Lymphoid Tissue Defects
      B and T cell deficiency
      hematopoietic development
      selective lymph node development defects
T Cell Receptor Signaling Defects
      B and T cell deficiency
      B and T cell deficiency, xenograft/transplant host

Internal/Organ Research
Adrenal Cortex Defects
      T cell deficiency
Lymphoid Tissue Defects
      B and T cell deficiency
      T cell deficiency
Thymus Defects
      B and T cell deficient

Research Tools
Cancer Research
      B and T cell deficiency, xenograft/transplant host
      B cell deficiency
      B, T, and NK cell deficiency, xenograft/transplant host
      T cell deficiency
      production of B and T cells, antibodies, and hybridomas
      production of T cells and hybridoma
      specific T cell deficiency
      xenograft/transplant host
Immunology, Inflammation and Autoimmunity Research
      B and T cell deficiency
      B cell deficiency
      B, T, and NK cell deficiency
      NK Cell Deficiency
      T cell deficiency
      T cell deficiency, xenograft/transplant host
      production of B cells and antibodies
      production of B cells, antibodies T cell lines, and hybridomas
      production of T cell lines and hybridomas
      specific T cell deficiency
Toxicology Research
      B and T cell deficiency, xenograft transplant host
      xenograft/transplant host

Virology Research
B and T Cell Deficiency
      AIDS research tool

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
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 Csf2/Il3tm1.1(CSF2,IL3)Flv
Allele Name targeted mutation 1.1, Richard A Flavell
Allele Type Targeted (Humanized sequence, Inserted expressed sequence)
Strain of OriginBALB/cAnNTac x 129S4/SvJae
Expressed Gene IL3, interleukin 3, human
Expressed Gene CSF2, colony stimulating factor 2 (granulocyte-macrophage), human
General Note Originally generated in ES cells containing Il2rgtm1.1Flv and Rag2tm1.1Flv.
Molecular Note The coding region of Il3 through Csf2 was replaced with the corresponding human sequence. The human Il3 remains under the control of the mouse promoter while expression of Csf2 is controlled by the human promoter. Cre-mediated recombination removed the selection cassettes. [MGI Ref ID J:168302]
 
 
Gene Symbol and Name Csf2, colony stimulating factor 2 (granulocyte-macrophage)
Chromosome 11
Gene Common Name(s) Csfgm; GMCSF; Gm-CSf; MGI-IGM; colony stimulating factor, granulocyte macrophage;
 
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) Ab2-183; 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]
 
Allele Symbol Thpotm1.1(TPO)Flv
Allele Name targeted mutation 1.1, Richard A Flavell
Allele Type Targeted
Common Name(s) TPOh;
Strain of OriginBALB/cAnNTac x 129S4/SvJae
Expressed Gene TPO, thyroid peroxidase, human
General Note Originally generated in ES cells containing Il2rgtm1.1Flv and Rag2tm1.1Flv.
Molecular Note The coding region was replaced with the corresponding human sequence. Cre-mediated recombination removed the neo cassette. [MGI Ref ID J:168301]
 
Gene Symbol and Name Thpo, thrombopoietin
Chromosome 16
Gene Common Name(s) MGDF; MKCSF; ML; MPLLG; Mpllg; THCYT1; TPO; TPO-1; TPO-2; TPO-3; TPO-4; myeloproliferative leukemia virus oncogene ligand;

Genotyping

Genotyping Information


Helpful Links

Genotyping resources and troubleshooting

References

References provided by MGI

Selected Reference(s)

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]

Additional References

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; 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]

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]

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]

Csf1tm1.1(CSF1)Flv related

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]

Csf2/Il3tm1.1(CSF2,IL3)Flv related

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]

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; 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]

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; 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]

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]

Thpotm1.1(TPO)Flv related

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]

Health & husbandry

Health & Colony Maintenance Information

Colony Maintenance

Breeding & HusbandryMITRG females homozygous for the five targeted mutations (i.e., MITRG homozygous females) are viable and fertile with a breeding lifespan of 6-8 months of age. MITRG males homozygous for the four somatic targeted mutations and hemizygous for the X-linked Il2rgtm1.1Flv mutation (i.e., MITRG homozygous males) are viable and fertile with a breeding lifespan of 6-8 months of age.
Therefore, the donating investigator maintains their MITRG colony by breeding MITRG homozygous females with MITRG homozygous males.
That is, in order of genomic location nomenclature, Rag2-/-;M-CSFh/h;IL-3/GM-CSFh/h;TPOh/h;γc-/- females with Rag2-/-;M-CSFh/h;IL-3/GM-CSFh/h;TPOh/h;γc-/Y males.
That is, in order of common name nomenclature, M-CSFh/h;IL-3/GM-CSFh/h;TPOh/h;Rag2-/-;γc-/- females with M-CSFh/h;IL-3/GM-CSFh/h;TPOh/h;Rag2-/-;γc-/Y males.

MITRG homozygous mice are immunodeficient. As such, and similar to other immunodeficient strains, maintenance in high health status (specific pathogen-free) vivaria promotes overall colony health. If MITRG homozygous animals are maintained in low health barrier rooms, the use of medicated water (e.g., sulfatrim/trimethoprim-sulfa or enrofloxacin/Baytril) is suggested to increase overall colony health.

Pricing and Purchasing

Pricing, Supply Level & Notes, Controls


 

This strain is currently Awaiting Transfer from the Donor.

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Live Mice

Price per Pair (US dollars $)Pair Genotype
$464.00Homozygous for Rag2tm1.1Flv, Homozygous for Csf1tm1.1(CSF1)Vlcg, Homozygous for Csf2/Il3tm1.1(CSF2,IL3)Flv, Homozygous for Thpotm1.1(TPO)Flv, Homozygous for Il2rgtm1.1Flv x Homozygous for Rag2tm1.1Flv, Homozygous for Csf1tm1.1(CSF1)Vlcg, Homozygous for Csf2/Il3tm1.1(CSF2,IL3)Flv, Homozygous for Thpotm1.1(TPO)Flv, Hemizygous Il2rgtm1.1Flv  

Standard Supply

Awaiting Transfer from the Donor

Pricing for International shipping destinations View USA Canada and Mexico Pricing

Live Mice

Price per Pair (US dollars $)Pair Genotype
$603.20Homozygous for Rag2tm1.1Flv, Homozygous for Csf1tm1.1(CSF1)Vlcg, Homozygous for Csf2/Il3tm1.1(CSF2,IL3)Flv, Homozygous for Thpotm1.1(TPO)Flv, Homozygous for Il2rgtm1.1Flv x Homozygous for Rag2tm1.1Flv, Homozygous for Csf1tm1.1(CSF1)Vlcg, Homozygous for Csf2/Il3tm1.1(CSF2,IL3)Flv, Homozygous for Thpotm1.1(TPO)Flv, Hemizygous Il2rgtm1.1Flv  

Standard Supply

Awaiting Transfer from the Donor

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Standard Supply

Awaiting Transfer from the Donor

Control Information

  Control
   See control note:

Depending upon the experiment, the following may be appropriate control strain(s):
--BALB/c;129 Rag2-;γc- (Stock No. 014593)
--BALB/c;129 Rag2-;γc-;TPOh (Stock No. 014594)
--BALB/c;129 Rag2-;γc-;IL-3/GM-CSFh (Stock No. 014595)
--BALB/c;129 Rag2-;γc-;CSF1h (Stock No. 017708)
--BALB/c;129 Rag2-;M-CSFh;IL-3/GM-CSFh;TPOh;γc-;hSIRPAtg (Stock No. 017712)

 
  Considerations for Choosing Controls
  Control Pricing Information for Genetically Engineered Mutant Strains.
 

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