Combined experience of six independent laboratories attempting to create an Ewing sarcoma mouse model.
Ewing sarcoma (ES) involves a tumor-specific chromosomal translocation that produces the EWS-FLI1 protein, which is required for the growth of ES cells both in vitro and in vivo. However, an EWS-FLI1-driven transgenic mouse model is not currently available. Here, we present data from six independent laboratories seeking an alternative approach to express EWS-FLI1 in different murine tissues. We used the Runx2, Col1a2.3, Col1a3.6, Prx1, CAG, Nse, NEFL, Dermo1, P0, Sox9 and Osterix promoters to target EWS-FLI1 or Cre expression. Additional approaches included the induction of an endogenous chromosomal translocation, in utero knock-in, and the injection of Cre-expressing adenovirus to induce EWS-FLI1 expression locally in multiple lineages. Most models resulted in embryonic lethality or developmental defects. EWS-FLI1-induced apoptosis, promoter leakiness, the lack of potential cofactors, and the difficulty of expressing EWS-FLI1 in specific sites were considered the primary reasons for the failed attempts to create a transgenic mouse model of ES.
['Minas|Tsion Zewdu|TZ|', 'Surdez|Didier|D|', 'Javaheri|Tahereh|T|', 'Tanaka|Miwa|M|', 'Howarth|Michelle|M|', 'Kang|Hong-Jun|HJ|', 'Han|Jenny|J|', 'Han|Zhi-Yan|ZY|', 'Sax|Barbara|B|', 'Kream|Barbara E|BE|', 'Hong|Sung-Hyeok|SH|', 'Çelik|Haydar|H|', 'Tirode|Franck|F|', 'Tuckermann|Jan|J|', 'Toretsky|Jeffrey A|JA|', 'Kenner|Lukas|L|', 'Kovar|Heinrich|H|', 'Lee|Sean|S|', 'Sweet-Cordero|E Alejandro|EA|', 'Nakamura|Takuro|T|', 'Moriggl|Richard|R|', 'Delattre|Olivier|O|', 'Üren|Aykut|A|']
D000256:Adenoviridae D000818:Animals D045744:Cell Line, Tumor D004195:Disease Models, Animal D015972:Gene Expression Regulation, Neoplastic D055879:Gene Knock-In Techniques D006801:Humans D051379:Mice D008822:Mice, Transgenic D009368:Neoplasm Transplantation D015514:Oncogene Proteins, Fusion D011401:Promoter Regions, Genetic D051789:Proto-Oncogene Protein c-fli-1 D034802:RNA-Binding Protein EWS D012512:Sarcoma, Ewing
Ewing sarcoma EWS-FLI1 EWS-FLI1 driven transgenic mouse model