title: Complicating the role of p53 in aging.
abstract: The p53 tumor suppressor protein plays a pivotal role in integrating various DNA damage response pathways and has been shown to be mutated in a variety of human cancers. In an effort to study the effects of a mutant p53 protein in a mouse model we generated a p53 targeting vector with a mutation in codon 245, equivalent to the mutational hot spot (codon 248) in humans. However, due to an aberrant gene targeting event in ES cells, we developed a p53 mutant mouse model that expressed a truncated p53 transcript that lacked the first six exons while retaining the intended mutation in exon 7. This mouse model was shown to exhibit serendipitous phenotypes that resembled premature aging as well as increased resistance to spontaneous tumors. Based on the genetic and molecular information available at that time, we hypothesized that the truncated p53 allele (m-allele) and its effect on wt p53 activity might be responsible for the observed phenotypes. However, the availability of the mouse genome data has allowed us to further characterize the genetic deletion present in the p53+/m mouse model. Our analyses indicate that there are 24 genes (including the p53 truncation) deleted in the p53+/m mouse model. These results suggest that the p53 tumor suppressor protein may not be solely responsible for the various phenotypes exhibited by p53+/m mouse model [corrected]
authors.affiliation: Department of Biochemistry and Cellular and Molecular Biology, University of Tennessee, Knoxville, TN 37996, USA.
authors.forename: Amanda
authors.initials: A
authors.lastname: Gentry
authors.forename: Sundaresan
authors.initials: S
authors.lastname: Venkatachalam
mesh_terms: D000375:Aging / Q000235:genetics*; D000818:Animals; D015139:Blotting, Southern; D016147:Genes, Tumor Suppressor / Q000502:physiology; D051379:Mice; D008817:Mice, Mutant Strains; D016159:Tumor Suppressor Protein p53 / Q000235:genetics*
chemical_list: D016159:Tumor Suppressor Protein p53