This NOD congenic strain contains a purinergic receptor P2X, ligand-gated ion channel, 7, P2rx7tm1Gab, targeted mutation. The P2x7 targeted mutation provides a tool to further dissect the interplay of ADP ribosylation and NAD-catabolizing enzymes and their effect on Tregs and iNKT involved in autoimmune type 1 diabetes.
Dr. David Serreze, The Jackson Laboratory
Christopher A. Gabel, Pfizer Pharmaceuticals
Genetic Background | Generation |
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|
Allele Type | Gene Symbol | Gene Name |
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Targeted (Modified isoform(s)) | P2rx7 | purinergic receptor P2X, ligand-gated ion channel, 7 |
Mice that are homozygous for the targeted allele and commonly referred to as NOD.P2X7, are viable, fertile, normal in size and do not display any gross physical or behavioral abnormalities. P2X7 located on chromosome 5 has been proposed as a candidate type 1 diabetes susceptibility gene.
On the C57BL/6 background, no gene product (mRNA or protein) is detected in cultured bone marrow mast cells or peritoneal macrophages. Samples of whole blood, as well as peritoneal macrophages, derived from mutant mice fail to produce extracellular interleukin 1 beta in response to lipopolysaccharide (LPS) and ATP treatment. Similarly, peritoneal lavage fluids from mutant animals that have been primed with LPS and subsequently challenged with ATP, are deficient in mature interleukin 1 beta, and at later time points, exhibit attenuated interleukin 6 levels when compared to fluids from similarly treated wildtype mice.
FACs analysis confirms P2X7 is absent on the surface of splenic T-cells of NOD.P2X7 homozygous mice. In addition, these splenic T-cells are resistant to NAD induced cell death. There are a greater number of splenic CD4+ iNKT-cells in NOD.P2X7 mice than NOD controls. There is no significant difference in diabetes onset between mutant and wildtype control mice. The presence of the P2X7 mutation combined with the Cd38 targeted mutation eliminates the accelerated diabetes seen in the NOD.Cd38 targeted mutation,
Stock No. 004311 - NOD.129P2(B6)-Cd38tm1Lnd/LtJ (Chen et al, 2011).
This strain maybe useful to further study the role of P2rx7 in type 1 diabetes studies and provides a tool to further dissect the interplay of ADP ribosylation and NAD-catabolizing enzymes and their effect on Tregs and iNKT involved in autoimmune type 1 diabetes.
A targeting vector containing a neomycin resistance gene driven by the mouse phosphoglycerate kinase promoter was used to disrupt the carboxyl-terminal coding region of the targeted gene. The construct was electroporated into 129P2/OlaHsd-derived E14TG2a embryonic stem (ES) cells. Correctly targeted ES cells were injected into C57BL/6 blastocysts and the progeny of the chimeric animals were maintained on a C57BL/6 background
(Stock No. 005576 - B6.129P2-P2rx7tm1Gab/J) prior to 9 backcross generations to NOD/ShiLtDvs. Using marker assisted technology, all known Idd loci were fixed to homozygosity. The congenic interval of this P2xr7 targeted mutation, located on chromosome 5, is less than 49Mb; with the proximal boundary located between D5Mit259 and P2xr7 and the distal boundary between D5Mit138 and D5Mit98. In 2011, the type 1 diabetes resource received this stock at generation N9F11.
Allele Name | targeted mutation 1, Christopher A Gabel |
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Allele Type | Targeted (Modified isoform(s)) |
Allele Synonym(s) | P2X7-; P2X7 KO; P2X7R-; P2X7RDelta506-532; Pfizer P2X7- |
Gene Symbol and Name | P2rx7, purinergic receptor P2X, ligand-gated ion channel, 7 |
Gene Synonym(s) | |
Strain of Origin | 129P2/OlaHsd |
Chromosome | 5 |
Molecular Note | Sequence encoding amino acids 506 through 532 was replaced by the insertion of a neomycin selection cassette. Transcript was undetected by Northern blot analysis of bone marrow mast cells isolated from homozygous mutant mice. Western blot analysis of homozygous mutant peritoneal macrophages showed an absence of normal and truncated protein. Subsequent analysis found low levels of expression of the 13b isoform in the brain, salivary gland and spleen as well as a C-terminal truncated variant transcript. |
Mutations Made By | Patrick Gillespie, Pfizer Pharmaceuticals |
When maintaining a live colony, these mice are bred as homozygotes
When using the NOD-P2rx7 mouse strain in a publication, please cite the originating article(s) and include JAX stock #015809 in your Materials and Methods section.
Facility Barrier Level Descriptions
Service/Product | Description | Price |
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Heterozygous and Wildtype for P2rx7<tm1Gab> |
Frozen Mouse Embryo | NOD.129P2(B6)-P2rx7<tm1Gab>/DvsJ Frozen Embryos | $2595.00 |
Frozen Mouse Embryo | NOD.129P2(B6)-P2rx7<tm1Gab>/DvsJ Frozen Embryos | $2595.00 |
Frozen Mouse Embryo | NOD.129P2(B6)-P2rx7<tm1Gab>/DvsJ Frozen Embryos | $3373.50 |
Frozen Mouse Embryo | NOD.129P2(B6)-P2rx7<tm1Gab>/DvsJ Frozen Embryos | $3373.50 |
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