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

骨肉瘤（osteosarcoma）转基因小鼠模型源自携带Tp53与Rb1基线缺失的成骨细胞（osteoblast cells）；然而该模型在骨肉瘤发生过程中并非100%外显，且未表现出可观测的转移性疾病征象。
为优化现有模型，研究人员引入第四等位基因，使得在他莫昔芬（tamoxifen）诱导的CreERT2介导重组作用下，成骨细胞内的Arid1a、Tp53及Rb1均可被条件性敲除。
研究人员对携带与不携带Arid1a的两个队列小鼠开展转录组水平比较，以明确Arid1a缺失所产生的生物学效应，以及与无Arid1a的高侵袭性转移性小鼠模型相关的信号通路。
实验设计：本研究对两个遗传队列的小鼠骨肉瘤样本进行对比分析：分别为OsxCreERT2+/-;p53fl/fl;Rb1fl/fl（非转移性）队列与OsxCreERT2+/-;p53fl/fl;Rb1fl/fl;Arid1afl/fl（转移性）队列，并通过RNA测序（RNA-seq）检测以鉴定基因表达差异。