Abstract
Known as the guardian of the genome, transformation-related protein 53 (TRP53) is a well -known tumor suppressor. Here, we describe a novel TRP53 deficient mouse model on a tumor prone background—SJL/J mice. The absence of TRP53 (TRP53 nullizygosity) leads to a shift in the tumor spectrum from a non-Hodgkin’s-like disease to thymic lymphomas and testicular teratomas at a very rapid tumor onset averaging ~12 weeks of age. In haplotype studies, comparing tumor prone versus tumor resistant Trp53 null mouse strains, we found that other tumor suppressor, DNA repair and/or immune system genes modulate tumor incidence in TRP53 null strains, suggesting that even a strong tumor suppressor such as TRP53 is modulated by genetic background. Due to their rapid development of tumors, the SJL/J TRP53 null mice generated here can be used as an efficient chemotherapy or immunotherapy screening mouse model.
Highlights
The product of the transformation-related protein (Trp53) is one of the most researched tumor suppressors in biomedical research, with currently more than 97,000 research/review articles published to date
Functional domains of transformation-related protein 53 (TRP53) are further downstream of this exon, targeting this exon to introduce a frame shift mutation is anticipated to lead to a null mutation
To generate p53 knockout alleles in the SJL/J mouse strain, superovulated female mice were mated and zygotes were collected for microinjection
Summary
The product of the transformation-related protein (Trp53) is one of the most researched tumor suppressors in biomedical research, with currently more than 97,000 research/review articles published to date. Known as the guardian of the genome, the function of TRP53 protein (TP53, or, in humans, p53) has been well studied, and its functions include transcriptional regulation, DNA repair, cell cycle check-point control, apoptosis, autophagy and senescence (for review, see [1,2,3,4,5,6,7,8,9]). The lack of a functional p53 gene product in humans leads to Li-Fraumeni syndrome predisposing the patient to a spectrum of early-onset cancers (for review, see [10,11,12]). Trp mutations have been shown to synergize with loss-of-function mutations in other tumor suppressor genes generally accelerating tumor development and progression. The disrupting of TRP53 has become a tool to accelerate the growth of tumors that develop from mutations in other tumor suppressor genes allowing more rapid and efficient study of these tumors
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