PD-1-/- mice display an increased infiltration of inflammatory cells in models of atherosclerosis, allograft vascular disease, encephalomyelitis, cardiomyopathy, and sepsis. They may be useful in applications related to the downregulation of T cell responses and inflammation.
Arlene H Sharpe, Harvard Medical School
PD-1-/- mice lack exons 2-3 of the programmed cell death 1 (Pdcd1) gene. Mice that are homozygous for this allele are viable and fertile.
PD-1 is an inhibitory cell surface receptor involved in the regulation of T-cell function during immunity and tolerance. PD-1 acts to down regulate the immune system by preventing the activation of T-cells. This reduces autoimmunity and promotes self-tolerance. Exons 2 and 3 encode the ligand binding and transmembrane domains of PD-1. These mice show an increase of Pou4f1+ retinal ganglion cells in the ganglion cell layer. These mice also display an increased infiltration of inflammatory cells in models of atherosclerosis, allograft vascular disease, encephalomyelitis, cardiomyopathy, and sepsis.
A targeting vector was designed to insert a loxP-flanked neomycin resistance (neo) cassette upstream of exon 2, and a single loxP site downstream of exon 3 of the programmed cell death 1 (Pdcd1) gene. The construct was electroporated into B6.Cg-derived Bruce 4 embryonic stem (ES) cells. Correctly targeted ES cells were transiently transfected with a Cre expression plasmid to delete the neo cassette and exons 2-3. Correctly targeted ES cells were injected into blastocysts and the donating investigator reported that the resulting PD-1-/- chimeric mice were bred with C57BL/6 mice for at least 15 generations. Upon arrival, mice were bred to C57BL/6J inbred mice (Stock No. 000664) for at least one generation to establish Stock No. 021157.
In 2016, the mice were further backcrossed to C57BL/6J using a marker-assisted approach to create this congenic line, Stock No. 28276. A high-density SNP marker panel shows that this strain is 99.65% congenic on C57BL/6J.
|Allele Name||targeted mutation 1.1, Arlene H Sharpe|
|Allele Type||Targeted (Null/Knockout)|
|Gene Symbol and Name||Pdcd1, programmed cell death 1|
|Strain of Origin||B6.Cg-Thy1a|
|Molecular Note||A floxed neo cassette was inserted upstream of exon 2 and an additional loxP site was inserted downstream of exon 3. Transient cre expression in ES cells removed exons 2 and 3 along with the neo cassette.|
When maintaining a live colony, homozygous mice may be bred together.
When using the PD-1- mouse strain in a publication, please cite the originating article(s) and include JAX stock #028276 in your Materials and Methods section.
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