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.
Of note, this allele is also being offered on a congenic C57BL/6J background as Stock No. 028276.
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/6J mice for at least 15 generations (please see SNP note below). Upon arrival, mice were bred to C57BL/6J inbred mice (Stock No. 000664) for at least one generation to establish the colony.
A 32 SNP (single nucleotide polymorphism) panel analysis, with 27 markers covering all 19 chromosomes and the X chromosome, as well as 5 markers that distinguish between the C57BL/6J and C57BL/6N substrains, was performed on the rederived living colony at The Jackson Laboratory Repository. Two the 27 markers throughout the genome are segregating, suggesting an incomplete backcross. 3 of 5 markers that determine C57BL/6J from C57BL/6N were found to be segregating. These data suggest the mice sent to The Jackson Laboratory Repository were on a mixed C57BL/6J ; C57BL/6N genetic background.
|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 #021157 in your Materials and Methods section.