Creation and preliminary characterization of a Tp53 knockout rat.

ABSTRACT: The tumor suppressor TP53 plays a crucial role in cancer biology, and the TP53 gene is the most mutated gene in human cancer. Trp53 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, resulting in a frameshift and premature terminations in the open reading frame. In cohorts of 25 homozygous (Tp53(?11/?11)), 37 heterozygous (Tp53(?11/+)) and 30 wild-type rats, the Tp53(?11/?11) rats lived an average of 126 days before death or removal from study because of clinical signs of abnormality or formation of tumors. Half of Tp53(?11/+) were removed from study by 1 year of age because of tumor formation. Both Tp53(?11/+) and Tp53(?11/?11) rats developed a wide spectrum of tumors, most commonly sarcomas. Interestingly, there was a strikingly high incidence of brain lesions, especially in Tp53(?11/?11) animals. We believe that this mutant rat line will be useful in studying cancer types rarely observed in mice and in carcinogenicity assays for drug development.

SUBMITTER: McCoy A 

PROVIDER: S-EPMC3529357 | biostudies-literature | 2013 Jan

REPOSITORIES: biostudies-literature