Abstract 2563: Characterization of a p53 knockout Sprague Dawley rat

Abstract

Abstract The tumor suppressor protein TP53 plays a crucial role in cancer biology, and the Tp53 gene is the most mutated gene in human cancer. The Tp53 knockout mouse models have been widely used in cancer etiology studies and in search for a cure of cancer with some limitations that other model organisms might help overcome. Via pronuclear microinjection of Zinc Finger Nucleases (ZFNs), we created a Tp53 knockout rat that contains an 11 bp deletion in exon 3. This deletion produces a frameshift and premature stop codons in the open reading frame. In cohorts of 30 homozygous, 35 heterozygous and 25 wild type rats, the homozygotes have an average life span of 126 days, and half of heterozygotes died by a year of age. Both heterozygous and homozygous knockouts developed a wide spectrum of tumors, most commonly, sarcomas. However, there is a strikingly high incidence of brain lesions, especially in homozygous animals. In addition, unlike the Tp53 knockout mice, both male and female homozygous Tp53 knockout rats are fertile. We believe this knockout rat line will be useful in studying cancer types rarely observed in mice and in carcinogenicity assays for drug development. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 2563. doi:1538-7445.AM2012-2563