NOD.Cg-Tnfrsf1b^tm1Imx Tnfrsf1a^tm1Imx/J

Stock number: 024314
Strain synonyms: NOD.TNFR1KO/TNFR2KO
Research areas: Apoptosis Research, Cancer Research, Diabetes and Obesity Research, Immunology, Inflammation and Autoimmunity Research

Description

These NOD.TNFR1KO/TNFR2KO double mutant mice exhibit resistance to spontaneous type 1 diabetes and have applications in studies of type 1 diabetes.

Detailed description

Mice that are homozygous for both targeted mutations are viable, fertile and completely resistant to spontaneous type 1 diabetes (in mice observed up to 30 weeks). When activated diabetogenic CD4+ T cells from NOD.Cg-Tg(TcraBDC2.5,TcrbBDC2.5)1Doi/DoiJ (Stock No. 004460)

are transferred to these NOD.TNFR1KO/TNFR2KO double mutant mice, diabetes development is delayed. Transfer of activated G9C8 clone cells (TCR from a CD8+ T cell clone specific for an insulin-derived peptide (InsB^15-23) bound to K^d MHC class I molecule) to the NOD.TNFR1KO/TNFR2KO mice, results in delayed diabetes development and only 75% of the mice developing diabetes.

In an attempt to offer alleles on well-characterized or multiple genetic backgrounds, alleles are frequently moved to a genetic background different from that on which an allele was first characterized. This is the case for the strain above. It should be noted that the phenotype could vary from that originally described. We will modify the strain description if necessary as published results become available.

Development

B6;129S-Tnfrsf1a^tm1Imx Tnfrsf1b^tm1Imx/J (Stock No. 003243) mice were backcrossed to NOD/ShiLtJ (Stock No. 001976) using a marker assisted protocol. The N5 backcrossed mice had no segregating markers outside of the Chromosome 4 and Chromosome 6 congenic regions.

Allele

Symbol: Tnfrsf1a^tm1Imx
Name: targeted mutation 1, Immunex Research and Development Corporation
MGI accession ID: MGI:1857468
Generation method: Targeted
Attributes: Null/Knockout
Marker symbol: Tnfrsf1a
Marker name: tumor necrosis factor receptor superfamily, member 1a
Chromosome: 6
Strain of origin: C57BL/6
Molecular note: A PGK-neomycin resistance cassette replaced 4kb of sequence, including exons 2 to 5 (amino acids 30 - 184). Lack of gene product was shown functionally.

Allele

Symbol: Tnfrsf1b^tm1Imx
Name: targeted mutation 1, Immunex Research and Development Corporation
MGI accession ID: MGI:1860087
Generation method: Targeted
Attributes: Null/Knockout
Marker symbol: Tnfrsf1b
Marker name: tumor necrosis factor receptor superfamily, member 1b
Chromosome: 4
Strain of origin: 129S7/SvEvBrd-Hprt1⁺
Molecular note: A PGK-neomycin resistance cassette replaced 1kb of sequence encoding amino acids 3 - 26. Lack of gene product was shown functionally.