Protein-level mutant p53 reporters identify druggable low-frequency precancerous clones in histologically normal tissues. Mus musculus

TP53 is the most important oncogene and is mutated in more than 50% of tumors. Mutant p53 (mut-p53) protein is not only highly accumulated in end-stage tumors, but also abundantly expressed in precancerous cells and early tumor samples. Due to the lack of mut-p53 reporter gene mice at the protein level, it is unclear what molecular characteristics mut-p53 hyperaccumulated cells have in vivo and how they malignantly transform into tumors. We constructed two mut-p53 transgenic mice by gene editing technology that mimic mut-p53 at the protein level and are able to specifically label early abnormal cells and end-stage tumor cells in a variety of tumors. Using mut-p53 dual reporter system and single cell analysis, we established the expression pattern of mut-p53 during tumor development, characterized the molecular features and dependent signaling pathways of early tumor cells and performed effective targeted interventions, demonstrating that these mouse models are promising for a wide range of applications in tumor research, especially tumorigenesis studies.