Description

The genotypes of the animals provided may not reflect those discussed in the strain description or the mating scheme utilized by The Jackson Laboratory prior to cryopreservation. Please inquire for possible genotypes for this specific strain.

Strain Information

Type Congenic; Mutant Strain; Targeted Mutation; Additional information on Genetically Engineered and Mutant Mice. Visit our online Nomenclature tutorial. Additional information on Congenic nomenclature. Species laboratory mouse Background Strain NOD/ShiLt Donor Strain 129S1 H2 Haplotype g7 Generation N8F11 (02-MAY-04) Generation Definitions   Donating Investigator David Serreze,   The Jackson Laboratory

Appearance
albino, pink eyed
Related Genotype: A/A Tyr^c/Tyr^c

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

Diabetes Mellitus, Insulin-Dependent; IDDM - Models with phenotypic similarity to human disease where etiologies are distinct.2

2 Human genes are associated with this disease. Orthologs of those genes do not appear in the mouse genotype(s).

View Mammalian Phenotype Terms

Mammalian Phenotype Terms provided by MGI

      assigned by genotype

Ifngr2^tm1Pbro/Ifngr2^tm1Pbro

        NOD.129S1-Ifngr2^tm1Pbro

• 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)

View Research Applications

Research Applications

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

Ifngr2^tm1Pbro related

Diabetes and Obesity Research
Type 1 Diabetes (IDDM)

Immunology and Inflammation 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 (knock-out)
Common Name(s)		IFN-gammaR2 -; IFNgammaRBnull; Ifngr2tm1Cmb;
Mutation Made By		Paul Rothman,   Columbia University
Strain of Origin		129S1/Sv-Oca2<+> Tyr<+> Kitl<+>
ES Cell Line Name		W9.5/W95
ES Cell Line Strain		129S1/Sv-Oca2<+> Tyr<+> Kitl<+>
Gene Symbol and Name		Ifngr2, interferon gamma receptor 2
Chromosome		16
Gene Common Name(s)		AF-1; IFGR2; IFNGT1; 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

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]

Ifngr2^tm1Pbro 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]

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]

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

Production of mice from cryopreserved embryos or sperm occurs in a maximum barrier room, RG10/RG30.

Purchasing information

Pricing, Supply Level & Notes, Controls

General Supply Notes

• This strain is included in the Type 1 Diabetes Repository collection.
• Genomic DNA is available for this strain from the Mouse DNA Resource.

Control Information

	Control
	001976 NOD/ShiLtJ
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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