Chromosomal translocations entail the generation of gene fusions in solid mesenchymal tumors. Despite the successful identification of these specific and consistent genetic events, the nature of the intimate association between the gene fusion and the resulting phenotype is pending to understand. Herein these studies are reviewed using FUS-CHOP as a model to illustrate how the manipulation of their loci in the mouse has contributed to the current understanding in unique and unexpected ways. FUS-CHOP is a chimeric oncogene generated by the most common chromosomal translocation t(12;16)(q13;p11) associated to liposarcomas. The application of transgenic methods to the study of this sarcoma-associated FUS-CHOP gene fusion has provided insights into their in vivo functions and suggested mechanisms by which lineage selection may be achieved.