Tissue-specific expression of p53 in transgenic mice is regulated by intron sequences

G Lozano1, A J Levine

  • 1Department of Molecular Genetics, University of Texas M. D. Anderson Cancer Center, Houston.

Molecular Carcinogenesis
|January 1, 1991
PubMed

Insights

Transgenic mice with a p53 cDNA construct showed no expression. However, including p53 introns, particularly intron 4, enabled transgene mRNA expression, especially in spleen cells.

Area of Science:

  • Molecular Biology
  • Genetics
  • Immunology

Background:

  • The p53 gene is a critical tumor suppressor involved in cellular responses to stress.
  • Understanding the regulation of p53 gene expression is crucial for cancer research.

Purpose of the Study:

  • To investigate the role of murine p53 introns in transgene expression in vivo.
  • To determine if intron 4 influences tissue-specific expression of p53.

Main Methods:

  • Generation of transgenic mice containing a p53 cDNA construct with SV40 regulatory elements.
  • Analysis of transgene mRNA expression in various tissues of the transgenic mice.
  • Evaluation of intron 4's effect on p53 mRNA levels and tissue preference.

Main Results:

  • The p53 cDNA construct alone was not expressed in transgenic mice.
  • The inclusion of murine p53 introns facilitated transgene mRNA expression in multiple tissues.
  • Intron 4 insertion led to preferential p53 mRNA expression in spleen cells, mirroring endogenous p53 expression patterns.
  • Intron 4 did not function as a transcriptional enhancer in cell culture or in vivo.

Conclusions:

  • Murine p53 introns are essential for the in vivo expression of the p53 transgene.
  • Intron 4 plays a significant role in regulating p53 mRNA levels and directing tissue-specific expression, particularly in the spleen.
  • These findings highlight the importance of intronic sequences in the post-transcriptional regulation of the p53 gene.

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