Exons 1b-6 of the killer cell lectin-like receptor subfamily K, member 1 (Klrk1) gene have been removed in these Klrk1-/- mice, abolishing gene expression. Klrk1 encodes NKG2D, a stimulatory immunoreceptor expressed by natural killer (NK) cells, activated CD8 T cells, certain CD4+ T cells, and subsets of gamma/delta and NK1.1+ T cells. NKG2D ligands are expressed during times of cellular stress, leaving cells susceptible to NK cell mediated lysis. As such, NKG2D has been associated with tumor surveillance, pathogen immunity, autoimmunity, and graft rejection. These Klrk1-/- mice contain normal numbers of NK cells and T cells in the spleen, bone marrow, lymph node, lung, and liver with reduced NKG2D expression. Subtle changes in expression of certain NK markers, including Ly49 receptors, were observed in the mutant mice. Klrk1+/- mice show a partial reduction in cell-surface expression of NKG2D, compared to wildtype mice, and exhibit some partial functional phenotypes. Homozygotes are viable and fertile.
When bred to C57BL/6-Tg(TRAMP)8247Ng/J mice (Stock No. 003135), a prostate cancer model, double mutant mice exhibited an increase in incident of highly aggressive malignant tumors. When bred to B6.Cg-Tg(IghMyc)22Bri/J mice (Stock No. 002728) the double mutant mice exhibited accelerated onset of tumorigenesis.
