FVB.129-Ets2^tm3Rgo/J

Stock number: 020455
Product name: Ets2^flox
Research areas: Cancer Research, Cell Biology Research, Immunology, Inflammation and Autoimmunity Research, Research Tools

Description

The Ets2^flox allele has loxP sites flanking the C-terminal portion of the E26 avian leukemia oncogene 2 DNA-binding domain (floxed exons 9-10). These Ets2^flox mice may be useful in studying both tumor repressive and tumor supportive roles in different types of cancer, epithelial tumor microenvironments, and endothelial cell function/survival during embryonic angiogenesis.

Detailed description

Homozygous Ets2^flox mice are viable and fertile. The Ets2^flox allele has loxP sites flanking exons 9-10 of the E26 avian leukemia oncogene 2 (Ets2) gene. When bred to mice that express Cre recombinase, the resulting offspring will have the sequences encoding the C-terminal portion of the Ets2 DNA-binding domain deleted in the cre-expressing tissues. This is designed to result in an inactive Ets2 protein lacking a functional DNA-binding domain (the deleted allele is called Ets2^db2).

When Ets2^flox mice are bred to mice with Cre recombinase expression in embryonic/germ cells (MORE-Cre; Stock No. 003755), the resulting homozygous mice with pan deletion of the Ets2 DNA binding domain exhibit embryonic lethality similar to Ets2 knockout mice. Furthermore, such mice may be used to study mammary epithelial tumor microenvironment when bred to also harbor transgenes expressing either Polyoma virus middle T antigen (see MMTV-PyVT mice [Stock No. 002374]) or activated Neu/ErbB2 (see MMTV-Neu/ErbB2 mice [Stock No. 005038]).

In addition, when Ets2^flox mice are bred to a strain expressing Cre recombinase in intestinal epithelial tissues (Villin-Cre; Stock No. 004586), the resulting mice are useful in studying intestinal stem cells, colon crypt development, and chemical carcinogen-induced colon tumorigenesis.

Development

A targeting vector was designed to insert an frt-flanked PGK-neo cassette and a loxP site upstream of exon 9, and a second loxP site downstream of exon 10 of the E26 avian leukemia oncogene 2 (Ets2) gene. The construct was electroporated into (129X1/SvJ x 129S1/Sv)F1-Kitl⁺-derived R1 embryonic stem (ES) cells. Correctly targeted ES cells were injected into recipient blastocysts and chimeric mice were bred with FVB/NJ mice to establish the Ets2^flox-neo colony. To remove the frt-flanked PGK-neo cassette, embryos from Ets2^flox-neo mice were isolated and then microinjected with a pCAGGS-Flpe plasmid. The resulting floxed exons 9-10 allele (a single frt site and first loxP site remaining upstream of exon 9, and a second loxP site downstream of exon 10) is called Ets2^flox. These Ets2^flox mice were subsequently backcrossed to FVB/NJ mice for at least nine generations prior to sending to The Jackson Laboratory Repository. Upon arrival, mice were bred to FVB/NJ inbred mice (Stock No. 001800) for at least one generation to establish The Jackson Laboratory Repository colony.

Allele

Symbol: Ets2^tm3Rgo
Name: targeted mutation 3, Robert G Oshima
MGI accession ID: MGI:3769393
Generation method: Targeted
Attributes: Conditional ready (e.g. floxed); No functional change
Marker symbol: Ets2
Marker name: E26 avian leukemia oncogene 2, 3' domain
Chromosome: 16
Strain of origin: (129X1/SvJ x 129S1/Sv)F1-Kitl⁺
Molecular note: An frt-flanked neo cassette with a 3' loxP site was inserted into intron 8 and an additional loxP site was inserted into the 3' UTR. The neo cassette was removed by flp-mediated recombination using a transiently expressing vector.