Healthy mice with an altered c-myc gene: role of the 3′ untranslated region revisited

• Published in: Oncogene Vol. 20; no. 32; pp. 4344 - 4353
• Main Authors: Langa, Francina, Lafon, Isabelle, Vandormael-Pournin, Sandrine, Vidaud, Michel, Babinet, Charles, Morello, Dominique
• Format: Journal Article
• Language: English
• Published: Basingstoke Nature Publishing 19.07.2001; Nature Publishing Group
• Subjects: 3' Untranslated Regions; Alleles; Animals; Apoptosis; Biological and medical sciences; c-myc gene; c-Myc protein; Cell culture; Cell cycle; Cell Differentiation; Cell Line; Fundamental and applied biological sciences. Psychology; Gene expression; Gene regulation; Gene Targeting; Genes; Genes, myc; Homologous recombination; Liver - physiology; Liver Regeneration; Mice; Mice, Transgenic; Molecular and cellular biology; mRNA; mRNA stability; Myc protein; Neomycin - biosynthesis; Neoplasms - etiology; Proteins; Proto-Oncogene Proteins c-myc - biosynthesis; Proto-Oncogene Proteins c-myc - genetics; Response Elements; RNA polymerase; RNA Stability; RNA, Messenger - biosynthesis; Sequence Deletion; Stem Cells - metabolism; Transgenic animals; France; Vertebrata; Mammalia; Healthy subject; Mouse; C-Onc gene; Rodentia; Transgenic animal; Gene therapy; Genetic transfer
• ISSN: 0950-9232; 1476-5594
• DOI: 10.1038/sj.onc.1204482

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.