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Related Concept Videos

Mouse Models of Cancer Study02:43

Mouse Models of Cancer Study

Mice have long served as models for studying human biology and pathology because of their phylogenetic and physiological similarity with humans. They are also easy to maintain and breed in the laboratory, and hence, many inbred strains are now available for research. Studies on mice have contributed immeasurably to our understanding of cancer biology.
The development of transgenic, knockout, and knock-in mice has led to an exponential increase in their use as model organisms in research,...
Mouse Models of Cancer Study02:43

Mouse Models of Cancer Study

Mice have long served as models for studying human biology and pathology because of their phylogenetic and physiological similarity with humans. They are also easy to maintain and breed in the laboratory, and hence, many inbred strains are now available for research. Studies on mice have contributed immeasurably to our understanding of cancer biology.
The development of transgenic, knockout, and knock-in mice has led to an exponential increase in their use as model organisms in research,...

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A Phenotyping Regimen for Genetically Modified Mice Used to Study Genes Implicated in Human Diseases of Aging
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Mouse models for the p53 R72P polymorphism mimic human phenotypes.

Feng Zhu1, Martijn E T Dollé, Thomas R Berton

  • 1Department of Carcinogenesis, Science Park-Research Division, The University of Texas MD Anderson Cancer Center, Smithville, Texas 78957, USA.

Cancer Research
|July 1, 2010
PubMed
Summary

The p53 R72P polymorphism influences apoptosis but not overall cancer development in mice. This study developed mouse models to investigate the functional impact of this common p53 gene variant.

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Area of Science:

  • Genetics
  • Molecular Biology
  • Cancer Research

Background:

  • The p53 tumor suppressor gene has a common single nucleotide polymorphism (SNP) at position 72, leading to arginine (R72) or proline (P72) variants.
  • This p53 R72P polymorphism affects p53's apoptotic activity, but its mechanistic basis and physiological relevance are not fully understood.

Purpose of the Study:

  • To develop and characterize mouse models for the p53 R72P single nucleotide polymorphism (SNP).
  • To investigate the functional consequences of the p53 R72 and p53 P72 variants on apoptosis and carcinogenesis.

Main Methods:

  • Development of mouse models expressing human or humanized p53 R72P variants.
  • Assessment of p53 target gene induction in response to DNA damage.
  • Evaluation of apoptotic responses to various stimuli and tumorigenic potential under chronic UV exposure.

Main Results:

  • The developed mouse models exhibit functional human or humanized p53 proteins, confirmed by gene induction and suppressed lymphomagenesis.
  • Mice with the 72R variant (p53R) showed a greater apoptotic response than those with the 72P variant (p53P).
  • Despite differential acute UV responses, no difference in tumorigenesis was observed between p53R and p53P mouse models after chronic UV exposure.

Conclusions:

  • The p53 R72P polymorphism modulates apoptosis through both transcriptional and non-transcriptional mechanisms.
  • The differential apoptotic activity associated with the p53 R72P polymorphism does not significantly impact carcinogenesis under the studied conditions.
  • These findings suggest that the functional impact of the p53 R72P SNP on cancer development may be context-dependent.