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

Oncotarget (2016-05-19)
Tsion Zewdu Minas, Didier Surdez, Tahereh Javaheri, Miwa Tanaka, Michelle Howarth, Hong-Jun Kang, Jenny Han, Zhi-Yan Han, Barbara Sax, Barbara E Kream, Sung-Hyeok Hong, Haydar Çelik, Franck Tirode, Jan Tuckermann, Jeffrey A Toretsky, Lukas Kenner, Heinrich Kovar, Sean Lee, E Alejandro Sweet-Cordero, Takuro Nakamura, Richard Moriggl, Olivier Delattre, Aykut Üren
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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KiCqStart® SYBR® Green qPCR ReadyMix, For Bio-Rad, Cepheid, Eppendorf, Illumina, Corbett, and Roche systems