huTP53 Mouse

The TRP53 (TP53 in humans) gene is a critical tumor suppressor gene that encodes the p53 protein, often called the "guardian of the genome." This protein is expressed at low levels in normal cells but becomes highly activated in response to various cellular stresses like DNA damage, hypoxia, and oncogene activation ^[1]. The p53 protein is a transcription factor that regulates a vast network of target genes, directing the cell's response to stress by inducing cell cycle arrest, DNA repair, apoptosis (programmed cell death), or senescence (permanent growth arrest). Its activity is crucial for maintaining genomic stability and preventing malignant transformation ^[2]. Mutations in TP53 are the most frequent genetic alterations in human cancers, found in over 50% of all malignancies. These mutations not only cause a loss of the protein's tumor-suppressing function but can also confer new, "gain-of-function" oncogenic properties that promote tumor growth, invasion, and metastasis. While most commonly associated with a wide range of cancers, including hereditary cancers like Li-Fraumeni syndrome, abnormal p53 activity has also been linked to non-neoplastic conditions such as certain developmental and neurodegenerative disorders, like Alzheimer's and Huntington's disease, and bone marrow failure syndrome. The p53 protein is expressed ubiquitously across most cellular tissues due to its fundamental role in cellular homeostasis ^[3].

huTP53 mouse is a humanized model constructed via gene editing technology, in which the region from ATG start codon to downstream of 3'UTR of mouse Trp53 is replaced with the region from ATG start codon to downstream of 3'UTR of human TP53. Initial research has shown that breeding the homozygous line results in a very small number of pups. While heterozygous females can breed normally, their maternal instincts are poor, with instances of cannibalism and occasional deaths of pups due to a failure to thrive. huTP53 mouse can be used for mechanistic research on a wide range of cancers, including hereditary cancers like Li-Fraumeni syndrome and preclinical studies of TP53-targeted drugs.