Abstract
c-Myc is a protooncogene involved in the control of cellular proliferation, differentiation and apoptosis. Like many other early response genes, regulation of c-myc expression is mainly controlled at the level of mRNA stability. Multiple cis-acting destabilizing elements have been described that are located both in the protein-coding region and in the 3′ untranslated region (3′ UTR). However, it is not known when they function during development and whether they act as partly redundant or independent elements to regulate c-myc mRNA level of expression. To begin to address these questions, we created a series of c-myc alleles modified in the 3′ UTR, using homologous recombination and the Cre/loxP system, and analysed the consequences of these modifications in ES cells and transgenic animals. We found that deletion of the complete 3′ UTR, including runs of Us and AU-rich elements proposed, on the basis of cell-culture assays, to be involved in the control of c-myc mRNA stability, did not alter the steady-state level of c-myc mRNA in any of the various situations analysed in vivo. Moreover, mice homozygous for the 3′ UTR-deleted gene were perfectly healthy and fertile. Our results therefore strongly suggest that the 3′ UTR of c-myc mRNA does not play a major role in the developmental control of c-myc expression.
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Acknowledgements
We thank A Bradley for the generous gift of c-myc plasmids and Y Lallemand and P Lonaï for pgk/Cre mice. We are grateful to M Poiret and J Auriol for technical assistance. We thank P Mercier, J Smith, F Pituello and A Vincent for critical reading of the manuscript. This work was supported by ARC n° 9842, La Ligue Nationale Contre le Cancer, CNRS, Institut Pasteur and MENRT.
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Langa, F., Lafon, I., Vandormael-Pournin, S. et al. Healthy mice with an altered c-myc gene: role of the 3′ untranslated region revisited. Oncogene 20, 4344–4353 (2001). https://doi.org/10.1038/sj.onc.1204482
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DOI: https://doi.org/10.1038/sj.onc.1204482
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