B6.129X1-Tnfsf8^tm1Pod/J

Stock number: 018588
Research areas: Immunology, Inflammation and Autoimmunity Research

Description

Mice that are homozygotes for this Tnfsf8 knockout strain are not as susceptible to graft versus host disease when compared to wildtype controls.

Detailed description

Mice that are homozygous for this knockout of Tnfsf8, tumor necrosis factor (ligand) superfamily, member 8 are viable and fertile. Tnfsf8 is expressed by activated CD4⁺ and CD8⁺ T cells, B cells, and macrophages, and has a role in Th17 cell differentiation. No gene product (mRNA or protein) is detected by RT PCR analysis of spleen cells (fresh and in vitro activated) isolated from homozygous animals. Homozygotes have decreased susceptibility to graft versus host disease, when compared to wildtype controls. Mutant mice are resistant to trinitrobenzene sulfonic acid (TNBS)-induced acute colitis, with reduced IFNG levels in the colonic lamina propria T cell. Homozygotes on the BALB/c background exhibit delayed bacterial clearance, impaired memory CD8+ T cell production, reduced sensitivity to OVA induced allergic rhinitis, resistance to dextran sulfate sodium (DSS) induced colitis and susceptibility to oxazolone (OXA)-induced colitis.

Development

A targeting vector containing a NEO cassette was used to replace 594 bp, including exon 1, of the targeted gene. The construct was electroporated into 129X1/SvJ derived RW-4 embryonic stem (ES) cells. Correctly targeted ES cells were injected into C57BL/6 blastocysts. The resulting male chimeric animals were crossed to C57BL/6 female mice. Heterozygotes were intercrossed to generate homozygotes. The mice were then backcrossed to C57BL/6J for at least 15 generations. Upon arrival at The Jackson Laboratory, the mice were crossed to C57BL/6J (Stock No. 000664) at least once to establish the colony.

Allele

Symbol: Tnfsf8^tm1Pod
Name: targeted mutation 1, Eckhard Podack
MGI accession ID: MGI:3054968
Generation method: Targeted
Attributes: Null/Knockout
Marker symbol: Tnfsf8
Marker name: tumor necrosis factor (ligand) superfamily, member 8
Chromosome: 4
Strain of origin: 129X1/SvJ
Molecular note: A targeting vector was designed to replace 594 bp, including exon 1, with a neo cassette. RT-PCR of spleen cells shows absence of wild-type transcript in mutant mice.