NOD.129S1(B6)-Ifngr2^tm1Pbro/DvsJ

Stock number: 004352
Strain synonyms: NOD.IFNRB^null
Research areas: Diabetes and Obesity Research, Immunology, Inflammation and Autoimmunity Research

Description

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.

Detailed 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)

Allele

Symbol: Ifngr2^tm1Pbro
Name: targeted mutation 1, Paul B Rothman
MGI accession ID: MGI:1930965
Generation method: Targeted
Attributes: Null/Knockout
Marker symbol: Ifngr2
Marker name: interferon gamma receptor 2
Chromosome: 16
Strain of origin: 129S1/Sv-Oca2⁺ Tyr⁺ Kitl⁺
Molecular note: Replacement of the second coding exon with a neomycin gene.