Tumor Development in P53 Knockout Mice: A Review of Mice Deficient For P53 - Tumor Development in P53 Knockout Mice: A Review of Mice Deficient For P53 - Open Access Pub

DOI10.14302/issn.2326-0793.jpgr-18-2422 Mice have been used as models of human disease because of their physiological and genetic similarities to humans 1. Since the development of the transgenic mouse in 1982 2, numerous manipulations of the mouse genome have been created to ultimately increase the understanding of human cancer. An initial study performed by Donehower et al. 3 introduced a null mutation of the human p53 suppressor gene into a normal p53 gene using homologous recombination. This was performed in mice embryonic stem cells to determine the role of the p53 in tumorigenesis and human malignancies. The gene encoding p53 is considered a tumor suppressor gene when it appears in its non-mutated form. However, when mutation or deletion of the gene occurs, it is thought to act as an oncogene, inducing the formation of tumors 4. Mutations and loss of the p53 gene have been linked to human tumor formations in a number of organs such as the lung, breast, colon, esophagus, liver, bladder, ovary and brain 5. Findings of p53 gene mutations have been associated with most human cancers and are connected to the tumors seen in human Li-Fraumeni syndrome, hereditary cancer vulnerability 6. Research on gene targeting in murine cells introduced the usage of mice as models for tumorigenesis and their importance in human tumorigenesis and cancer. Understanding these concepts in mice increases the possibility for cancer discoveries in humans. By linking the p53 gene to tumorigenesis and cancers, further studies have been developed to associate the effect of a null or mutated p53 gene in very specific cell types. The null mutations of the p53 gene are essential when examining human tumorigenesis and cancers, and could contribute to the understanding of the formation of diseases and possible effective treatment approaches. An example of a study that elaborates on the research shows the effects of a mutated p53 gene that were isolated to mammary epithelium in an attempt to examine its role in murine mammary tumorigenesis 7. This is useful as a model for breast cancer 8. The mice carrying the mutant p53 gene successfully showed how a null tumor suppressor gene affects tumor development 9. The results from this study were successful in comparing tumor formation in the different strains of mice. It was shown that wild type mice did not develop any tumors by the age of nine months, while cancerous tumor developments were extremely notable in mutant p53 homozygous mice. Of the 35 p53 homozygotic mice assessed, 74 percent developed abnormal growth of body tissue and