B6J.B6N(Cg)-Ncr1^{tm1.1(icre/ERT2)Tfen}/J

Stock number: 041348
Product name: Ncr1-iCreER^T2
Research areas: Hematological Research, Immunology, Inflammation and Autoimmunity Research, Research Tools

Description

Ncr1-iCreER^T2 mice have a codon-improved tamoxifen-inducible cre/ERT2 fusion gene inserted in the 3' UTR of the Ncr1 gene. This model is useful when studying cellular dynamics within the NKp46+ innate lymphoid cell compartment.

Detailed description

Ncr1-iCreER^T2 knock-in mice express a codon-improved tamoxifen-inducible cre/ERT2 fusion gene under the control of the endogenous natural cytotoxicity triggering receptor 1 (Ncr1) promoter. Ncr1 encodes the activating receptor NKp46, which is expressed specifically on the surface of natural killer (NK) cells and possibly on related innate lymphocytes. It plays a crucial role in the immune system's ability to recognize and kill tumor cells, infected cells, and pathogens.

When these Ncr1-iCreER^T2 mice are bred with mice containing loxP-flanked sequences, tamoxifen-inducible Cre-mediated recombination will result in deletion of floxed sequences in NKp46+ cells. When bred to R26R-EYFP mice (Stock No. 006148), removal of the floxed STOP cassette results in yellow fluorescent protein expression in the NKp46+ cells of the blood, spleen, and liver, as well as BM and lymph nodes (LN) in resulting Ncr1-iCreER^T2 x Rosa26YFP^LSL mice after tamoxifen treatment. Expression is restricted to NKp46+ cells, and no expression is evident in other hematopoietic lineages, including T cells.

Development

The Ncr1-iCreER^T2 targeting vector contains a P2A self-cleaving peptide sequence (P2A) and an icre/ERT2 fusion gene (codon-improved Cre recombinase fused to a human estrogen receptor ligand binding domain) inserted into the 3' UTR of the natural cytotoxicity triggering receptor 1 (Ncr1) gene. An FRT-flanekd neomycin resistance (neo) cassette was inserted downstream of the icre/ERT2 sequence. The construct was electroporated into B6N-derived B6/BLU embryonic stem (ES) cells. Correctly targeted ES cells were injected into blastocysts. The resulting Ncr1-iCreER^T2 mice were bred to mice expressing FLP recombinase on a C57BL/6J genetic background to removed the neo cassette, and resulting mice were further backcrossed to C57BL/6J mice (Stock No. 000664) for at least 20 generations by the donating laboratory. Upon arrival at The Jackson Laboratory, sperm was cryopreserved. To establish our live colony, an aliquot of frozen sperm was used to fertilize C57BL/6J oocytes.

Allele

Symbol: Ncr1^{tm1.1(icre/ERT2)Tfen}
Name: targeted mutation 1.1, Todd A Fehniger
MGI accession ID: MGI:6739825
Generation method: Targeted
Attributes: Recombinase-expressing; Inducible
Synonyms: Ncr1^{tm1(icre/ERT2)Tfen}; Ncr1-iCreER^T2
Marker symbol: Ncr1
Marker name: natural cytotoxicity triggering receptor 1
Marker synonyms: CD335; KILR-1; Ly94; MAR1 (mouse activating receptor 1); Nkp46; NK-p46
Chromosome: 7
Strain of origin: C57BL/6NTac-Tg(HBB-lacZ)ALey/Ley
Molecular note: Via homologous recombination in ES cells, the targeting vector inserted tamoxifen-responsive iCreERT2 cassette into the Ncr1 locus linked to the C-terminal translation via a P2A ribosomal skip site. An FRT-flanekd neomycin resistance (neo) cassette was inserted downstream of the icre/ERT2 sequence. Cre recombinase to removed the neo cassette.