RGD Reference Report - Rats deficient for p53 are susceptible to spontaneous and carcinogen-induced tumorigenesis. - Rat Genome Database

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Rats deficient for p53 are susceptible to spontaneous and carcinogen-induced tumorigenesis.

Authors: Yan, He-Xin  Wu, Hong-Ping  Ashton, Charles  Tong, Chang  Ying, Qi-Long 
Citation: Yan HX, etal., Carcinogenesis. 2012 Oct;33(10):2001-5. doi: 10.1093/carcin/bgs238. Epub 2012 Jul 12.
RGD ID: 12792958
Pubmed: PMID:22791818   (View Abstract at PubMed)
PMCID: PMC3499043   (View Article at PubMed Central)
DOI: DOI:10.1093/carcin/bgs238   (Journal Full-text)

The p53 tumor suppressor gene is highly mutated in human cancers. Individuals who inherit one p53 mutant allele are susceptible to a wide range of tumor types, including breast cancer and sarcoma. We recently generated p53 knockout rats through gene targeting in embryonic stem cells. Here we show that rats homozygous for the null allele are prone to early onset spontaneous sarcomas and lymphoma with high incidence of metastases. Heterozygous rats are also highly predisposed to cancer, but with a delayed onset and a wider spectrum of tumor types compared with homozygotes. Importantly, up to 20% of female heterozygotes developed breast cancer and about 70% of the tumors were positive for estrogen receptor. Exposing p53-deficient rats to a low dose of the carcinogen diethylnitrosamine dramatically decreased the latency for sarcoma development and survival time compared with equivalently treated wild-type rats. These unique features make this knockout line a valuable model for investigating human malignancy and in vivo carcinogenicity of chemicals and therapeutic compounds.



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STOCK-Tp53tm1(EGFP-Pac)Qly/Rrrc  (p53 knockout rat)


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