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.
