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Creation and preliminary characterization of a Tp53 knockout rat
Aaron McCoy1, Cynthia L Besch-Williford, Craig L Franklin
1Sigma Advanced Genetic Engineering Labs, Sigma-Aldrich Corporation, St Louis, MO 63146, USA.
Disease Models & Mechanisms
|August 25, 2012
Summary
A new Tp53 knockout rat model was developed to study cancer. These rats develop a wide spectrum of tumors, including sarcomas and brain lesions, offering new research avenues.
Area of Science:
- Oncology
- Genetics
- Animal Models
Background:
- The TP53 gene is frequently mutated in human cancers.
- Trp53 knockout mouse models are used in cancer research but have limitations.
- Alternative model organisms may overcome limitations in current cancer models.
Purpose of the Study:
- To create and characterize a Tp53 knockout rat model for cancer research.
- To evaluate the utility of this rat model in studying cancer etiology and drug development.
Main Methods:
- Zinc finger nucleases (ZFNs) were used for pronuclear microinjection to create the knockout.
- An 11-bp deletion in exon 3 of the Tp53 gene resulted in a frameshift mutation.
- Homozygous (Tp53(Δ11/Δ11)), heterozygous (Tp53(Δ11/+)), and wild-type rat cohorts were studied.
Main Results:
- Tp53(Δ11/Δ11) rats had an average lifespan of 126 days due to tumors or clinical abnormalities.
- Half of Tp53(Δ11/+) rats developed tumors by 1 year of age.
- Both knockout genotypes developed diverse tumors, primarily sarcomas, with a high incidence of brain lesions in homozygous rats.
Conclusions:
- The Tp53 knockout rat is a valuable model for studying various cancer types, including those rare in mice.
- This model can be utilized for carcinogenicity assays in drug development.
- The high incidence of brain lesions warrants further investigation.
