PDL1-/-.NOD NSG mice are NOD/LtJ-congenic animals carrying the PD-L1- (Cd274-) knockout mutation that have been backcrossed to NSG mice (Stock No. 005557).
Arlene H Sharpe, Harvard Medical School
Genetic Background | Generation |
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|
Allele Type | Gene Symbol | Gene Name |
---|---|---|
Spontaneous | Prkdc | protein kinase, DNA activated, catalytic polypeptide |
Allele Type | Gene Symbol | Gene Name |
---|---|---|
Targeted (Null/Knockout) | Il2rg | interleukin 2 receptor, gamma chain |
Allele Type | Gene Symbol | Gene Name |
---|---|---|
Targeted (Null/Knockout) | Cd274 | CD274 antigen |
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. On the NSG background, mice should be immunodeficient. They should have no mature T cells or B cells, lack functional natural killer (NK) cells, have reduced numbers of lymphocytes and myeloid dendritic cells, and be deficient in cytokine signaling.
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 of these congenic mice could vary from that originally described. We may modify the strain description if necessary as published results become available.
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 and are maintained as 018307. Some mice were also backcrossed to NSG mice (Stock No. 005557) and are maintained as this Stock No. 027905.
Allele Name | severe combined immunodeficiency |
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Allele Type | Spontaneous |
Allele Synonym(s) | SCID |
Gene Symbol and Name | Prkdc, protein kinase, DNA activated, catalytic polypeptide |
Gene Synonym(s) | |
Site of Expression | T and B lymphocytes. |
Strain of Origin | C.BKa-Ighb/Icr |
Chromosome | 16 |
Molecular Note | A T-to-A transversion point mutation at a position corresponding to codon 4046 (codon 4095 in transcript ENSMUST00000023352.8) created a premature stop codon (p.Y4046*). |
Allele Name | targeted mutation 1, Warren J Leonard |
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Allele Type | Targeted (Null/Knockout) |
Allele Synonym(s) | [KO]gammac; CD132-; gammac-; gc-; Il2rgtm1Wjll; IL2Rgammanull |
Gene Symbol and Name | Il2rg, interleukin 2 receptor, gamma chain |
Gene Synonym(s) | |
Site of Expression | Primarily lymphoid cells. |
Strain of Origin | 129S4/SvJae |
Chromosome | X |
Molecular Note | A neomycin resistance cassette replaced part of exon 3 and all of exons 4 - 8 of the gene, resulting in the loss of most of the extracellular domain and all of the transmembrane and cytoplasmic domains of the protein. |
Mutations Made By | Dr. Warren Leonard, NHLBI, NIH |
Allele Name | targeted mutation 1, Arlene H Sharpe |
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Allele Type | Targeted (Null/Knockout) |
Allele Synonym(s) | PD-L1- |
Gene Symbol and Name | Cd274, CD274 antigen |
Gene Synonym(s) | |
Strain of Origin | C57BL/6 |
Chromosome | 19 |
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. |
When maintaining the live congenic colony, females that are homozygous for Prkdcscid and Il2rgtm1Wjl are bred to males that are homozygous for Prkdcscid and hemizygous for Il2rgtm1Wjl (Il2rg is an X-linked gene). Cd274tm1Shr allele should be maintained as heterozygous in the colony due to lethality issues.
When using the NSG.PDL1- mouse strain in a publication, please cite the originating article(s) and include JAX stock #027905 in your Materials and Methods section.
Facility Barrier Level Descriptions
Service/Product | Description | Price |
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Homozygous for Prkdc<scid>, heterozygous or wildtype for Cd274<tm1Shr>, homoygous females and hemizygous male for Il2rg<tm1Wjl> |
Frozen Mouse Embryo | NOD.Cg-Prkdc<scid> Cd274<tm1Shr> Il2rg<tm1Wjl>/J | $2595.00 |
Frozen Mouse Embryo | NOD.Cg-Prkdc<scid> Cd274<tm1Shr> Il2rg<tm1Wjl>/J | $2595.00 |
Frozen Mouse Embryo | NOD.Cg-Prkdc<scid> Cd274<tm1Shr> Il2rg<tm1Wjl>/J | $3373.50 |
Frozen Mouse Embryo | NOD.Cg-Prkdc<scid> Cd274<tm1Shr> Il2rg<tm1Wjl>/J | $3373.50 |
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The Jackson Laboratory has rigorous genetic quality control and mutant gene genotyping programs to ensure the genetic background of JAX® Mice strains as well as the genotypes of strains with identified molecular mutations. JAX® Mice strains are only made available to researchers after meeting our standards. However, the phenotype of each strain may not be fully characterized and/or captured in the strain data sheets. Therefore, we cannot guarantee a strain's phenotype will meet all expectations. To ensure that JAX® Mice will meet the needs of individual research projects or when requesting a strain that is new to your research, we suggest ordering and performing tests on a small number of mice to determine suitability for your particular project. We do not guarantee breeding performance and therefore suggest that investigators order more than one breeding pair to avoid delays in their research.
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