B6.129X1-Ebi3^tm1Rsb/J

Stock number: 008691
Product name: EBI3-
Research areas: Cancer Research, Cell Biology Research, Immunology, Inflammation and Autoimmunity Research, Internal/Organ Research, Research Tools

Description

These mutant mice harbor a knockout of the Epstein-Barr virus induced gene 3 (Ebi3) and may be useful in studying Foxp3⁺ regulatory T cell (T_reg) function, IL12 heterodimeric cytokines (such as IL-35 and IL-27), IFNgamma production, and Th1/Th2 immune responses (including inflammatory bowel disease).

Detailed description

Mice homozygous for this Ebi3-mutant allele are viable and fertile with the donating investigator reporting no overt autoimmunity or inflammatory disease associated with the mutation. No RNA from the targeted gene is observed in splenocytes isolated from homozygotes. Ebi3-deficiency leads to impaired T_reg activity with failure to control homeostatic proliferation. Homozygotes exhibit decreased numbers and function of invariant natural killer T cells (iNKT); stimulated iNKT cells show impaired IL-4 production both in vivo and in vitro. Homozygotes are resistant to oxazolone-induced colitis (mediated primarily by T helper (Th) 2-type cytokine production by iNKT cells), whereas Ebi3-deficiency shows no affect on trinitrobenzene sulfonic acid-induced colitis (a predominantly Th1-mediated colitis model). These Ebi3-mutant strains may be useful in studying T_reg function, IL12 heterodimeric cytokines (such as IL-35 and IL-27),IFNgamma production, and Th1/Th2 immune responses (including inflammatory bowel disease).

Of note, Ebi3-mutant mice are also be available on a BALB/c congenic background (see Stock No. 008701).

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. 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

The targeting vector was designed to replace exons 2-5 (encoding amino acids 24-228) of the targeted gene with a PGK-Neo cassette. The donating investigators lab reports that the construct was electroporated into 129X1/SvJ-derived RW4 embryonic stem (ES) cells. Correctly targeted ES cells were injected into blastocysts and offspring from the resulting chimeric mice were bred to C57BL/6NCrl inbred mice. Ebi3-mutant mice were then backcrossed to C57BL/6NCrl for at least 9 generations prior to arrival at The Jackson Laboratory. Upon arrival, mice were bred to C57BL/6NJ inbred mice (Stock No. 005304) for at least one generation to establish the current colony.

Allele

Symbol: Ebi3^tm1Rsb
Name: targeted mutation 1, Richard Blumberg
MGI accession ID: MGI:2448308
Generation method: Targeted
Attributes: Null/Knockout
Marker symbol: Ebi3
Marker name: Epstein-Barr virus induced gene 3
Chromosome: 17
Strain of origin: 129X1/SvJ
Molecular note: Sequence encompassing exons 2 through 5 was replaced by a neomycin selection cassette inserted by homologous recombination. Northern blot analysis of splenic RNA indicated an absence of normal transcript in homozygous mutant mice.