- Minas, Tsion Zewdu;
- Surdez, Didier;
- Javaheri, Tahereh;
- Tanaka, Miwa;
- Howarth, Michelle;
- Kang, Hong-Jun;
- Han, Jenny;
- Han, Zhi-Yan;
- Sax, Barbara;
- Kream, Barbara E;
- Hong, Sung-Hyeok;
- Çelik, Haydar;
- Tirode, Franck;
- Tuckermann, Jan;
- Toretsky, Jeffrey A;
- Kenner, Lukas;
- Kovar, Heinrich;
- Lee, Sean;
- Sweet-Cordero, E Alejandro;
- Nakamura, Takuro;
- Moriggl, Richard;
- Delattre, Olivier;
- Üren, Aykut
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.