NOD.Cg-Prkdc^scid Cd274^tm1Shr Il2rg^tm1Wjl/J

Stock number: 027905
Product name: NSG.PDL1-
Research areas: Cancer Research, Cell Biology Research, Hematological Research, Immunology, Inflammation and Autoimmunity Research, Internal/Organ Research, Research Tools, Virology Research

Description

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).

Detailed description

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.

Development

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

Symbol: Prkdc^scid
Name: severe combined immunodeficiency
MGI accession ID: MGI:1857113
Generation method: Spontaneous
Marker symbol: Prkdc
Marker name: protein kinase, DNA activated, catalytic polypeptide
Chromosome: 16
Strain of origin: C.BKa-Igh^b/Icr
Site of expression: T and B lymphocytes.
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

Symbol: Il2rg^tm1Wjl
Name: targeted mutation 1, Warren J Leonard
MGI accession ID: MGI:1857455
Generation method: Targeted
Attributes: Null/Knockout
Marker symbol: Il2rg
Marker name: interleukin 2 receptor, gamma chain
Chromosome: X
Strain of origin: 129S4/SvJae
Site of expression: Primarily lymphoid cells.
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.

Allele

Symbol: Cd274^tm1Shr
Name: targeted mutation 1, Arlene H Sharpe
MGI accession ID: MGI:3050803
Generation method: Targeted
Attributes: Null/Knockout
Marker symbol: Cd274
Marker name: CD274 antigen
Chromosome: 19
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.