B6.129-Gt(ROSA)26Sor^{tm1(TMPRSS2/ERG)Key}/J

Stock number: 024512
Product name: Rosa26^ERG/ERG
Research areas: Cancer Research, Developmental Biology Research, Internal/Organ Research, Reproductive Biology Research, Research Tools

Description

Rosa26^ERG mice conditionally expresses the human ERG transcription factor after Cre-mediated excision of a loxP-flanked STOP sequence. It is useful in studying ETS-mediated prostate oncogenesis.

Detailed description

Translocation of ETS transcription factors ERG (avian erythroblastosis virus E-26 (v-ets) oncogene related), ETV1, ETV4, EV5, and FLI1 occur in half of all prostate cancers. TMPRSS2 (transmembrane protease, serine 2)-ERG translocation is the most common molecular alteration.

These Rosa26^ERG mice conditionally express the TMPRSS2-ERG fusion transcription factor as well as a nuclear-localized EGFP from the Gt(ROSA26)Sor gene after cre-mediated excision of a loxP-flanked Stop sequence. When crossed into probasin (Pbsn)-cre, ERG is specifically and strongly expressed in the prostate, causing a low penetrance of prostate hyperplasia. When bred with Pbsn-cre and Pten floxed mice (to knock out PTEN expression in the prostate), ERG expression causes accelerated, highly penetrant invasive prostate cancer in the progeny. Triple mutant mice show invasive adenocarcinoma characterized by small irregular glandular structures composed of malignant cells with large, pleiomorphic nuclei and pale cytoplasm developed adjacent to prostatic intraepithelial neoplasia by 8 weeks of age. By 6 months, approximately 80% of these mice contain regions of adenocarcinoma with enlarged, hardened prostates.

EGFP expression can be detected directly or through immunohistochemistry.

Development

A splice acceptor (SA), PGK-neomycin and 4x-polyA transcriptional Stop between reverse orientation loxP sites, TMPRSS2 (non-coding human exon 1)-ERG (exon 4) cDNA, IRES-EGFP with 3 nuclear localization sequences (nls), and a polyA tail were inserted into intron 1 of the non-coding Gt(ROSA)26Sor gene. The targeting vector was introduced to 129-derived embryonic stem (ES) cells. This strain was backcrossed to C57BL/6 for 6 generations by the donating laboratory.

Allele

Symbol: Gt(ROSA)26Sor^{tm1(TMPRSS2/ERG)Key}
Name: targeted mutation 1, Charles L Sawyers
MGI accession ID: MGI:5524275
Generation method: Targeted
Attributes: Conditional ready (e.g. floxed); Inserted expressed sequence; Humanized sequence
Marker symbol: Gt(ROSA)26Sor
Marker name: gene trap ROSA 26, Philippe Soriano
Chromosome: 6
Strain of origin: 129
Expressed genes: TMPRSS2,transmembrane serine protease 2,human; ERG,ETS transcription factor ERG,human; GFP,Green Fluorescent Protein,
Site of expression: EGFP and the TMPRSS2-ERG fusion transcription factor will be expressed in cells where promoters driving Cre recombinase are expressed.
Molecular note: The targeting construct introduced into the locus a splice acceptor sequence, floxed neomycin resistance STOP (4x polyadenylation sequence) cassette, fusion of human TMPRSS2 (exon 1) and ERG (exon 4), IRES, nuclear localized EGFP and polyadenylation sequence.