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Combined experience of six independent laboratories attempting to create an Ewing sarcoma mouse model

Tsion Zewdu Minas 1 Didier Surdez 2, 3 Tahereh Javaheri 4 Miwa Tanaka 5 Michelle Howarth 6 Hong-Jun Kang 7 Jenny Han 1 Zhi-yan Han 2, 3 Barbara Sax 4 Barbara E Kream 8 Sung-Hyeok Hong 1 Haydar Çelik 1 Franck Tirode 2, 3 Jan Tuckermann 9 Jeffrey A Toretsky 1 Lukas Kenner 4, 10, 11 Heinrich Kovar 12, 13 Sean Lee 7 E. Alejandro Sweet-Cordero 6 Takuro Nakamura 5 Richard Moriggl 4, 14, 15 Olivier Delattre 2, 3, 16, * Aykut Üren 1 
Abstract : 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.
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Tsion Zewdu Minas, Didier Surdez, Tahereh Javaheri, Miwa Tanaka, Michelle Howarth, et al.. Combined experience of six independent laboratories attempting to create an Ewing sarcoma mouse model. Oncotarget, Impact journals, 2016, 8 (21), pp.34141 - 34163. ⟨10.18632/oncotarget.9388⟩. ⟨inserm-02440436⟩



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