Strain Name:

NOD.129S1(B6)-Ifngr2tm1Pbro/DvsJ

Stock Number:

004352

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Availability:

Repository- Live

These Ifngr2 knock-out mice produce more IFNG and significantly more Il4 than NOD controls when stimulated with cultured T cells in vitro with anti-CD3.

Description

Strain Information

Type Congenic; Mutant Strain; Targeted Mutation;
Additional information on Genetically Engineered and Mutant Mice.
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Additional information on Congenic nomenclature.
Mating SystemHomozygote x Homozygote         (Female x Male)   03-MAY-13
Specieslaboratory mouse
Background Strain NOD/ShiLt
Donor Strain 129S1
H2 Haplotypeg7
GenerationN8F11p+F2 (03-DEC-13)
Generation Definitions
 
Donating InvestigatorDr. David Serreze,   The Jackson Laboratory

Appearance
albino, pink eyed
Related Genotype: A/A Tyrc/Tyrc

Description
Although Ifngr2 deficient mice on the NOD/Lt background are defective in Ifng induced gene expression, they exhibit no significant difference in leukocyte subset (CD4 positive T cells, CD8 positive T cells, B cells, macrophages, dendritic cells, and granulocutes) as compared to NOD/Lt controls. Upon stimulation of cultured T cells in vitro with anti-CD3, Ifngr2 deficient NOD mice produce more IFNG and significantly more Il4 than NOD controls. Ifngr2 mutant mice develop IDDM at a similar rate as NOD/Lt controls (85% female incidence after 30 weeks in mutant mice versus 100% female incidence in standard NOD/Lt controls). (Serreze et al 2000)

Development
To disrupt the Th1/Th2 signaling function of IFNG, without affecting the other functions of IFNG, the Ifngr2 gene was disrupted. A replacement vector of 11 kb including the Ifngr2 gene was derived from a 129/Sv genomic library and the second exon was replaced by a neomycin resistence cassette. After transfection, correctly targeted W9.5 ES cells (derived from 129S1/Sv-p+ Tyr+ Kitl+) were injected into C57BL/6 blastocysts and resulting heterozygous chimeric mice were intercrossed to create homozygous Ifngr2 deficient mice. The disrupted Ifngr2 gene was then congenically transferred to the NOD/Lt background using a marker assisted protocol. NOD/Lt mice heterozygous for the Ifngr2 mutation and homozygous for diabetes susceptibility loci (Idd) were intercrossed at N8 to develop mice homozygous for the mutation and all Idd loci. (Lu et al 1998; Serreze et al 2000)

Control Information

  Control
   001976 NOD/ShiLtJ
 
  Considerations for Choosing Controls

Related Strains

Strains carrying other alleles of Ifngr2
004970   B6.Cg-Tg(CD2-Ifngr2)1Pbro/Dvs
004551   NOD.Cg-Tg(CD2-Ifngr2)2Pbro/DvsJ
View Strains carrying other alleles of Ifngr2     (2 strains)

Phenotype

Phenotype Information

View Related Disease (OMIM) Terms

Related Disease (OMIM) Terms provided by MGI
- Model with phenotypic similarity to human disease where etiologies are distinct. Human genes are associated with this disease. Orthologs of these genes do not appear in the mouse genotype(s).
Diabetes Mellitus, Insulin-Dependent; IDDM
- Potential model based on gene homology relationships. Phenotypic similarity to the human disease has not been tested.
Immunodeficiency 28; IMD28   (IFNGR2)
View Mammalian Phenotype Terms

Mammalian Phenotype Terms provided by MGI
      assigned by genotype

Ifngr2tm1Pbro/Ifngr2tm1Pbro

        NOD.129S1-Ifngr2tm1Pbro
  • immune system phenotype
  • abnormal T-helper 2 physiology
    • enhanced Th2 responses   (MGI Ref ID J:65986)
  • abnormal cytotoxic T cell physiology
    • CD8+ T cells injected into Ifngr2-deficient NOD mice are less able to cause diabetes, due to impaired homing ability and impaired diapedesis   (MGI Ref ID J:72818)
  • decreased susceptibility to autoimmune diabetes
    • when diabetogenic splenocytes are injected into Ifngr2-deficient NOD mice, diabetes development is delayed compared to wild-type NOD mice   (MGI Ref ID J:72818)
  • homeostasis/metabolism phenotype
  • *normal* homeostasis/metabolism phenotype
    • unexpectedly, incidence of type 1 diabetes in females was unchanged   (MGI Ref ID J:65986)
  • hematopoietic system phenotype
  • abnormal T-helper 2 physiology
    • enhanced Th2 responses   (MGI Ref ID J:65986)
  • abnormal cytotoxic T cell physiology
    • CD8+ T cells injected into Ifngr2-deficient NOD mice are less able to cause diabetes, due to impaired homing ability and impaired diapedesis   (MGI Ref ID J:72818)
View Research Applications

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

Ifngr2tm1Pbro related

Diabetes and Obesity Research
Type 1 Diabetes (IDDM)

Immunology, Inflammation and Autoimmunity Research
Immunodeficiency
Inflammation

Genes & Alleles

Gene & Allele Information provided by MGI

 
Allele Symbol Ifngr2tm1Pbro
Allele Name targeted mutation 1, Paul B Rothman
Allele Type Targeted (Null/Knockout)
Common Name(s) IFN-gammaR2 -; IFNgammaRBnull; Ifngr2tm1Cmb;
Mutation Made By Paul Rothman,   Columbia University
Strain of Origin129S1/Sv-Oca2<+> Tyr<+> Kitl<+>
ES Cell Line NameW9.5/W95
ES Cell Line Strain129S1/Sv-Oca2<+> Tyr<+> Kitl<+>
Gene Symbol and Name Ifngr2, interferon gamma receptor 2
Chromosome 16
Gene Common Name(s) AF-1; IFGR2; IFNGT1; IMD28; Ifgr2; Ifgt; interferon gamma transducer;
Molecular Note Replacement of the second coding exon with a neomycin gene. [MGI Ref ID J:48016]

Genotyping

Genotyping Information

Genotyping Protocols

Generic Neo Melt Curve Analysis, Melt Curve Analysis
Ifngr2tm1Pbro, Standard PCR


Helpful Links

Genotyping resources and troubleshooting

References

References provided by MGI

Selected Reference(s)

Serreze DV; Post CM; Chapman HD; Johnson EA; Lu B; Rothman PB. 2000. Interferon-gamma receptor signaling is dispensable in the development of autoimmune type 1 diabetes in NOD mice. Diabetes 49(12):2007-11. [PubMed: 11118001]  [MGI Ref ID J:65986]

Additional References

Lu B; Ebensperger C; Dembic Z; Wang Y; Kvatyuk M; Lu T; Coffman RL; Pestka S; Rothman PB. 1998. Targeted disruption of the interferon-gamma receptor 2 gene results in severe immune defects in mice. Proc Natl Acad Sci U S A 95(14):8233-8. [PubMed: 9653170]  [MGI Ref ID J:48016]

Savinov AY; Wong FS; Chervonsky AV. 2001. IFN-gamma Affects Homing of Diabetogenic T Cells. J Immunol 167(11):6637-43. [PubMed: 11714835]  [MGI Ref ID J:72818]

Serreze DV; Chapman HD; Varnum DS; Hanson MS; Reifsnyder PC; Richard SD; Fleming SA; Leiter EH; Shultz LD. 1996. B lymphocytes are essential for the initiation of T cell-mediated autoimmune diabetes: analysis of a new speed congenic stock of NOD.Ig mu null mice. J Exp Med 184(5):2049-53. [PubMed: 8920894]  [MGI Ref ID J:37287]

Ifngr2tm1Pbro related

Cain JA; Smith JA; Ondr JK; Wang B; Katz JD. 2006. NKT cells and IFN-gamma establish the regulatory environment for the control of diabetogenic T cells in the nonobese diabetic mouse. J Immunol 176(3):1645-54. [PubMed: 16424194]  [MGI Ref ID J:126603]

Calderon B; Carrero JA; Miller MJ; Unanue ER. 2011. Cellular and molecular events in the localization of diabetogenic T cells to islets of Langerhans. Proc Natl Acad Sci U S A 108(4):1561-6. [PubMed: 21220322]  [MGI Ref ID J:168246]

Calderon B; Carrero JA; Miller MJ; Unanue ER. 2011. Entry of diabetogenic T cells into islets induces changes that lead to amplification of the cellular response. Proc Natl Acad Sci U S A 108(4):1567-72. [PubMed: 21220309]  [MGI Ref ID J:168247]

Fallarino F; Bianchi R; Orabona C; Vacca C; Belladonna ML; Fioretti MC; Serreze DV; Grohmann U; Puccetti P. 2004. CTLA-4-Ig activates forkhead transcription factors and protects dendritic cells from oxidative stress in nonobese diabetic mice. J Exp Med 200(8):1051-62. [PubMed: 15492127]  [MGI Ref ID J:93957]

Fang Y; Yu S; Braley-Mullen H. 2012. TGF-beta Promotes Proliferation of Thyroid Epithelial Cells in IFN-gamma(-/-) Mice by Down-Regulation of p21 and p27 via AKT Pathway. Am J Pathol 180(2):650-60. [PubMed: 22119715]  [MGI Ref ID J:180437]

Haring JS; Badovinac VP; Olson MR; Varga SM; Harty JT. 2005. In vivo generation of pathogen-specific Th1 cells in the absence of the IFN-gamma receptor. J Immunol 175(5):3117-22. [PubMed: 16116201]  [MGI Ref ID J:113254]

Horie I; Abiru N; Sakamoto H; Iwakura Y; Nagayama Y. 2011. Induction of autoimmune thyroiditis by depletion of CD4+CD25+ regulatory T cells in thyroiditis-resistant IL-17, but not interferon-gamma receptor, knockout nonobese diabetic-H2h4 mice. Endocrinology 152(11):4448-54. [PubMed: 21862617]  [MGI Ref ID J:178345]

Lu B; Ebensperger C; Dembic Z; Wang Y; Kvatyuk M; Lu T; Coffman RL; Pestka S; Rothman PB. 1998. Targeted disruption of the interferon-gamma receptor 2 gene results in severe immune defects in mice. Proc Natl Acad Sci U S A 95(14):8233-8. [PubMed: 9653170]  [MGI Ref ID J:48016]

Mori Y; Kodaka T; Kato T; Kanagawa EM; Kanagawa O. 2009. Critical role of IFN-gamma in CFA-mediated protection of NOD mice from diabetes development. Int Immunol 21(11):1291-9. [PubMed: 19778991]  [MGI Ref ID J:154177]

Savinov AY; Wong FS; Chervonsky AV. 2001. IFN-gamma Affects Homing of Diabetogenic T Cells. J Immunol 167(11):6637-43. [PubMed: 11714835]  [MGI Ref ID J:72818]

Yi Z; Li L; Garland A; He Q; Wang H; Katz JD; Tisch R; Wang B. 2012. IFN-gamma receptor deficiency prevents diabetes induction by diabetogenic CD4+, but not CD8+, T cells. Eur J Immunol 42(8):2010-8. [PubMed: 22865049]  [MGI Ref ID J:187880]

Yu S; Sharp GC; Braley-Mullen H. 2006. Thyrocytes responding to IFN-gamma are essential for development of lymphocytic spontaneous autoimmune thyroiditis and inhibition of thyrocyte hyperplasia. J Immunol 176(2):1259-65. [PubMed: 16394017]  [MGI Ref ID J:126438]

Health & husbandry

Health & Colony Maintenance Information

Animal Health Reports

Room Number           AX18

Colony Maintenance

Mating SystemHomozygote x Homozygote         (Female x Male)   03-MAY-13
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 $239.00Female or MaleHomozygous for Ifngr2tm1Pbro  
Price per Pair (US dollars $)Pair Genotype
$478.00Homozygous for Ifngr2tm1Pbro x Homozygous for Ifngr2tm1Pbro  

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 $310.70Female or MaleHomozygous for Ifngr2tm1Pbro  
Price per Pair (US dollars $)Pair Genotype
$621.40Homozygous for Ifngr2tm1Pbro x Homozygous for Ifngr2tm1Pbro  

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.

General Supply Notes

Control Information

  Control
   001976 NOD/ShiLtJ
 
  Considerations for Choosing Controls
  Control Pricing Information for Genetically Engineered Mutant Strains.
 

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