Homozygous and heterozygous p53 knockout rats develop metastasizing sarcomas with high frequency.
Am J Pathol
; 179(4): 1616-22, 2011 Oct.
Article
in En
| MEDLINE
| ID: mdl-21854749
ABSTRACT
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.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Sarcoma
/
Tumor Suppressor Protein p53
/
Gene Knockout Techniques
/
Heterozygote
/
Homozygote
Limits:
Animals
/
Female
/
Humans
/
Male
Language:
En
Journal:
Am J Pathol
Year:
2011
Document type:
Article
Affiliation country:
Netherlands