B6.Cg-Klrk1^tm1Dhr/J

Stock number: 022733
Product name: Klrk1^-
Strain synonyms: NKG2D-
Research areas: Apoptosis Research, Cancer Research, Immunology, Inflammation and Autoimmunity Research, Research Tools

Description

These Klrk1 knock-out mice exhibit subtle changes in the expression of certain NK cell regulatory molecules. They are suitable for use in applications related to the study of NK cell-mediated lysis.

Detailed description

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.

Development

A targeting vector was designed to replace exons 1b-6 of the killer cell lectin-like receptor subfamily K, member 1 (Klrk1) gene with a loxP-flanked neomycin resistance (neo) cassette. The construct was electroporated into C57BL/6-derived Bruce-4 embryonic stem (ES) cells. Correctly targeted ES cells were injected into BALB/c blastocysts and resulting chimeric males were bred to C57BL/6J females. Heterozygous offspring were bred with CMV-Cre transgenic mice, on a congenic C57BL/6J background, to delete the neo cassette. Progeny were crossed to C57BL/6J remove the Cre-expressing transgene. These mice were bred to C57BL/6J mice for at least 3 generations. Upon arrival, mice were bred to C57BL/6J inbred mice (Stock No. 000664) for at least one generation to establish the colony.

Allele

Symbol: Klrk1^tm1Dhr
Name: targeted mutation 1, David H Raulet
MGI accession ID: MGI:3790957
Generation method: Targeted
Attributes: Null/Knockout
Marker symbol: Klrk1
Marker name: killer cell lectin-like receptor subfamily K, member 1
Chromosome: 6
Strain of origin: B6.Cg-Thy1^a
Molecular note: Exons 1b through exon 6 were replaced by a floxed neomycin resistance cassette through homologous recombination. Mice carrying germline mutations were crossed with a cre transgenic mouse strain to remove the neomycin selection cassette, leaving a single loxP site behind. Gene inactivation was confirmed by a lack of protein staining on NK cells using flow cytometry.