FVB.Cg-Klrk1^tm1Dhr/J

Stock number: 025662
Research areas: Apoptosis Research, Cancer Research, Immunology, Inflammation and Autoimmunity Research, Research Tools

Description

These Klrk1 knock-out mice may be useful for studying NK cell-mediated lysis, and cancer onset and progression.

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. Homozygotes are viable and fertile.

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 could vary from that originally described. We will modify the strain description if necessary as published results become available.

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, and subsequently to FVB mice for at least 10 generations. Upon arrival, mice were bred to FVB/NJ inbred mice (Stock No. 001800) 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
Synonyms: NKG2D^-
Marker symbol: Klrk1
Marker name: killer cell lectin-like receptor subfamily K, member 1
Marker synonyms: CD314; D12S2489E; D6H12S2489E; KLR; Nkg2d; NKG2-D; Nkrp2
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.