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Type of publication: Journal Article
Type of document: Full Paper

Year: 2017

Authors: Minas, TZ; Surdez, D; Javaheri, T; Tanaka, M; Howarth, M; Kang, HJ; Han, J; Han, ZY; Sax, B; Kream, BE; Hong, SH; Çelik, H; Tirode, F; Tuckermann, J; Toretsky, JA; Kenner, L; Kovar, H; Lee, S; Sweet-Cordero, EA; Nakamura, T; Moriggl, R; Delattre, O; Üren, A

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

Source: Oncotarget. 2017; 8(21):34141-34163

Authors Vetmeduni Vienna:

Kenner Lukas
Moriggl Richard

Vetmed Research Units
Institute of Pathology, Pathology of Laboratory Animals
Institute of Animal Breeding and Genetics, Unit for Functional Cancer Genomics

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.

Keywords Pubmed: Adenoviridaegenetics
Cell Line, Tumor
Disease Models, Animal
Gene Expression Regulation, Neoplastic
Gene Knock-In Techniques
Mice, Transgenic
Neoplasm Transplantation
Oncogene Proteins, Fusiongenetics
Promoter Regions, Genetic
Proto-Oncogene Protein c-fli-1genetics
RNA-Binding Protein EWSgenetics
Sarcoma, Ewinggeneticspathology

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