Homozygous and heterozygous p53 knockout rats develop metastasizing sarcomas with high frequency

Ruben van Boxtel, Raoul V Kuiper, Pim W Toonen, Sebastiaan van Heesch, Roel Hermsen, Alain de Bruin, Edwin Cuppen

Onderzoeksoutput: Bijdrage aan tijdschriftArtikelpeer review

27 Citaten (Scopus)

Samenvatting

The TP53 tumor suppressor gene is mutated in the majority of human cancers. Inactivation of p53 in a variety of animal models results in early-onset tumorigenesis, reflecting the importance of p53 as a gatekeeper tumor suppressor. We generated a mutant Tp53 allele in the rat using a target-selected mutagenesis approach. Here, we report that homozygosity for this allele results in complete loss of p53 function. Homozygous mutant rats predominantly develop sarcomas with an onset of 4 months of age with a high occurrence of pulmonary metastases. Heterozygous rats develop sarcomas starting at 8 months of age. Molecular analysis revealed that these tumors exhibit a loss-of-heterozygosity of the wild-type Tp53 allele. These unique features make this rat highly complementary to other rodent p53 knockout models and a versatile tool for investigating tumorigenesis processes as well as genotoxic studies.

Originele taal-2Engels
Pagina's (van-tot)1616-22
Aantal pagina's7
TijdschriftThe American journal of pathology
Volume179
Nummer van het tijdschrift4
DOI's
StatusGepubliceerd - okt. 2011
Extern gepubliceerdJa

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