Immunized CD274 (PD-L1) knockout mice develop severe EAE. Mice exhibit resistance to Leishmania mexicana and a decrease in IL4 producing cells (suggesting an impaired Th2 response) and increased interferon gamma production under certain conditions. This strain may be useful in studies of T cell regulation, activation and tolerance.
Arlene H Sharpe, Harvard Medical School
Homozygotes: Mice that are homozygous for the targeted mutation are viable, fertile, normal in size and do not display any gross physical or behavioral abnormalities. CD4+ T cells exhibit increased interferon gamma production in vivo when stimulated with low anti-CD3 concentrations; CD8+ T cells exhibit increased interferon gamma production, but only when stimulated with higher antibody concentrations, in both cases, T cell proliferation is not effected. OVA primed CD8+ T cells produce 5-10 fold more interferon gamma than controls. T cell clonal expansion is augmented and cytolysis is increased in mutant antigen-specific CD8+ T cells. Unlike experimental immune encephalitis (EAE) resistant 129S4/SvJae mice, immunized mutant mice on the 129S4/SvJae background develop severe EAE with early onset and rapid progression. Mice exhibit resistance to Leishmania mexicana and a decrease in IL4 producing cells, suggesting an impaired Th2 response. This mutant mouse strain may be useful in studies of T cell regulation, activation and tolerance.
Heterozygote: no phenotype
A targeting vector containing neomycin resistance and herpes simplex virus thymidine kinase genes was used to replace the signal exon and two thirds of the IgV exon. The construct was electroporated into 129S4/SvJae derived J1 embryonic stem (ES) cells. Correctly targeted ES cells were injected into blastocysts. The resulting chimeric animals were crossed to 129S4/SvJae mice and heterozygotes interbred to generate homozygotes. Upon arrival, mice were bred to 129S4/SvJaeJ for at least 1 generation to establish the colony.
|Allele Name||targeted mutation 2, Arlene H Sharpe|
|Allele Type||Targeted (Null/Knockout)|
|Gene Symbol and Name||Cd274, CD274 antigen|
|Strain of Origin||129S4/SvJae|
|Molecular Note||A neomycin resistance gene replaced the signal exon and two-thirds of the IgV exon. Southern blot confirmed recombination.|
|Mutations Made By|| |
Arlene Sharpe, Harvard Medical School
While maintaining a live colony, these mice are bred as homozygotes.
When using the PD-L1- mouse strain in a publication, please cite the originating article(s) and include MMRRC stock #32234 in your Materials and Methods section.