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.
Dr. David Serreze, The Jackson Laboratory
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)
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)
|Allele Name||targeted mutation 1, Paul B Rothman|
|Allele Type||Targeted (Null/Knockout)|
|Allele Synonym(s)||IFN-gammaR2 -; IFNgammaRBnull; Ifngr2tm1Cmb|
|Gene Symbol and Name||Ifngr2, interferon gamma receptor 2|
|Strain of Origin||129S1/Sv-Oca2+ Tyr+ Kitl+|
|Molecular Note||Replacement of the second coding exon with a neomycin gene.|
|Mutations Made By|| |
Paul Rothman, Johns Hopkins University
When using the NOD.129S1(B6)-Ifngr2tm1Pbro/DvsJ mouse strain in a publication, please cite the originating article(s) and include JAX stock #004352 in your Materials and Methods section.