The Fusion Oncogene FUS-CHOP Drives Sarcomagenesis of High-Grade Spindle Cell Sarcomas in Mice

Figure 1

Vector targeting strategies for generation of Rosa26 LSL-FUS-CHOP/+ mice. (a) The LSL-FUS-CHOP vector was designed to target the Rosa26 locus. The human 7-2 FUS-CHOP cDNA is under the control of an EF1α promoter and a floxed STOP (LSL) cassette that prevents expression in the absence of Cre-mediated recombination. A woodchuck hepatitis virus (WHV) posttranscriptional regulatory element with a polyadenylation signal (WPRE-pA) was placed downstream of the FUS-CHOP cDNA to enhance transgene expression. A Neo selection cassette flanked by attB and attP sites was included in the targeting vector for ES cell selection. The Neo cassette can be deleted by PhiC31-mediated recombination of the attB and attP sites. Cre recombinase excises the STOP cassette and activates FUS-CHOP expression. (b) Genotyping of chimeric mice generated via ES cell injection. (c) Genotyping of pups to determine germline transmission in chimeras. Mouse 147 is a founder mouse that has the LSL-FUS-CHOP targeting vector in its germline.

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