PDL1-/-.NOD mice are NOD/LtJ-congenic animals homozygous for the PD-L1- (Cd274-) knockout mutation. PDL1-/-.NOD mice develop accelerated diabetes as early as four weeks of age in both females and males. Homozygous mice have abnormal T cell morphology and physiology.
Arlene H Sharpe, Harvard Medical School
The signal and all of the immunoglobulin (Ig)-V-like exon of the CD274 antigen (Cd274) gene were replaced with a neomycin resistance cassette, abolishing PD-L1 gene expression. PD-L1 is one of two ligands for PD-1 and is upregulated on antigen presenting cells (APCs), activated T cells, myeloid cells, dendritic cells (DCs). It is also expressed on hematopoietic and parenchymal cells. PD-1 is an inhibitory receptor expressed on activated lymphocytes, regulates tolerance and autoimmunity by negative regulation of T cell responses. These mice are more susceptible to T cell-mediated tissue damage from autoimmune diabetes. They get accelerated diabetes after 2 generations of NOD backcrossing. All mice display accelerated diabetes between 4-7 weeks of age. When treated with anti-CD3 these mice develop a wasting disease between 12 and 20 weeks of age characterized by sudden deterioration, weight loss, and inflammation in the heart and skeletal muscles. This wasting disease leads to death within 3-5 days of development of illness. As homozygotes develop diabetes early, this line should be maintained as heterozygotes, although they also develop diabetes.
A targeting vector was designed to replace the signal and all of the immunoglobulin (Ig)-V-like exon of the CD274 antigen (Cd274) gene with a neomycin resistance cassette. This construct was electroporated into C57BL/6-derived embryonic stem (ES) cells and correctly targeted ES cells were injected into blastocysts. The resulting chimeric animals were bred together to generate a colony of PD-L1- mice. The mutant mice were then backcrossed with NOD/LtJ inbred mice for at least 15 generations. The donating investigator reports that these mice are confirmed homozygous for Idd 1, 2, 3, 4, 5a, 5d, 7, 8, 9, 10, 11, 12, 13, 14, 15 loci after speed congenic backcross to NOD/LtJ. Upon arrival at The Jackson Laboratory Repository, mice were bred to NOD/ShiLtJ inbred mice (Stock No. 001976) for at least one generation.
Of note, this allele is also available for engraftment studies on the on the immunodeficient NSG background (Stock No. 027905).
|Allele Name||targeted mutation 1, Arlene H Sharpe|
|Allele Type||Targeted (Null/Knockout)|
|Allele Synonym(s)||Cd274tm1Shr; targeted mutation 1, Arlene H Sharpe|
|Gene Symbol and Name||Cd274, CD274 antigen|
|Gene Synonym(s)||B7-H1; B7H1; Pdcd1lg1; programmed cell death 1 ligand 1; PDL1; PD-L1; PDCD1LG1; RGD1566211; PDCD1L1; B7-H; Pdcd1lg1; hPD-L1|
|Strain of Origin||C57BL/6|
|Molecular Note||The signal and all of the IgV exon was replaced with a neomycin resistance gene. Southern blot confirmed recombination. Flow cytometry showed lack of expression in B cells, T cells, macrophages or DCs in mutants.|
PDL1-deficient mice on NOD background (PDL1-/-.NOD) get accelerated diabetes as early as four weeks of age. When maintaining a live colony, heterozygous females may be bred with heterozygous males.
When using the PDL1-.NOD mouse strain in a publication, please cite the originating article(s) and include JAX stock #018307 in your Materials and Methods section.
|Heterozygous or wildtype for Cd274<tm1Shr>|
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