Evaluating the impact that Arid1a deletion has on the transcriptional differences between two murine models of osteosarcoma
Transgenic mouse models of osteosarcoma originate from osteoblast cells with a baseline deletion of Tp53 and Rb1; however, the model is not 100% penetrant in osteosarcomagenesis and demonstrates no visible evidence of the metastatic disease. To enhance the current model, a fourth allele was added so that Arid1a, Tp53, and Rb1 are all conditionally deleted in osteoblast cells upon tamoxifen-induced, CreERT2-mediated recombination. Mice from both cohorts, with and without Arid1a were compared at the transcriptional level to identify the consequences of Arid1a deletion and the pathways associated with the more aggressive and metastatic mouse model without Arid1a. Overall design: We compared murine osteosarcomas from two genetic cohorts: OsxCreERT2+/-;p53fl/fl;Rb1fl/fl (non-metastatic) and OsxCreERT2+/-;p53fl/fl;Rb1fl/fl;Arid1afl/fl (metastatic) and performed RNA-seq to identify differences in gene expression