Trp53, an ortholog of the human TP53 gene, is a crucial tumor suppressor gene. Its protein product, p53, plays extensive roles as the "guardian of the genome," regulating the cell cycle, DNA repair, apoptosis, cellular metabolism, and senescence, thus balancing cell death and proliferation [3]. Genetic models, like knockout mice, are valuable for studying Trp53.

In Trp53 knockout mouse models, several significant findings have emerged. BALB/c-Trp53-deficient mice show a delayed involution phenotype and a mammary tumor phenotype, enhancing our understanding of p53's role in involution, its hormonal regulation, and its cooperation with other oncogenic pathways in mammary tumorigenesis [2]. Also, dual loss of Rb1 and Trp53 in the mouse adrenal medulla leads to spontaneous pheochromocytomas, suggesting Trp53 is an efficient genetic modifier of Rb1 loss in the development of this tumor [4]. In the Trp53+/- mouse model used for short-term carcinogenicity testing, these mice respond positively to genotoxic carcinogens, negatively to non-genotoxic rodent carcinogens and non-carcinogens, indicating this assay is not overly sensitive [1].

In conclusion, Trp53 is essential for maintaining genomic stability and preventing tumorigenesis. The study of Trp53 using gene knockout mouse models has provided insights into its role in various biological processes and disease conditions, particularly in breast cancer, pheochromocytoma development, and carcinogenicity testing [1,2,3,4].

References:

1. Floyd, Eugenia, Mann, Peter, Long, Gerald, Ochoa, Ricardo. . The Trp53 hemizygous mouse in pharmaceutical development: points to consider for pathologists. In Toxicologic pathology, 30, 147-56. doi:. https://pubmed.ncbi.nlm.nih.gov/11890468/

2. Blackburn, Anneke C, Jerry, D Joseph. 2002. Knockout and transgenic mice of Trp53: what have we learned about p53 in breast cancer? In Breast cancer research : BCR, 4, 101-11. doi:. https://pubmed.ncbi.nlm.nih.gov/12052252/

3. Merino, Diana, Malkin, David. . p53 and hereditary cancer. In Sub-cellular biochemistry, 85, 1-16. doi:10.1007/978-94-017-9211-0_1. https://pubmed.ncbi.nlm.nih.gov/25201186/

4. Tonks, Ian D, Mould, Arne W, Schroder, Wayne A, Walker, Graeme J, Kay, Graham F. . Dual loss of rb1 and Trp53 in the adrenal medulla leads to spontaneous pheochromocytoma. In Neoplasia (New York, N.Y.), 12, 235-43. doi:. https://pubmed.ncbi.nlm.nih.gov/20234817/