N-myc can functionally replace c-myc in murine development, cellular growth, and differentiation

Barbara A. Malynn, Ignacio Moreno De Alboran, Rónán C. O'Hagan, Roderick Bronson, Laurie Davidson, Ronald A. DePinho, Frederick W. Alt

Research output: Contribution to journalArticlepeer-review

263 Scopus citations

Abstract

Members of the myc family of cellular oncogenes have been implicated as transcriptional regulators in pathways that govern cellular proliferation and death. In addition, N-myc and c-myc are essential for completion of murine embryonic development. However, the basis for the evolutionary conservation of myc gene family has remained unclear. To elucidate this issue, we have generated mice in which the endogenous c-myc coding sequences have been replaced with N-myc coding sequences. Strikingly, mice homozygous for this replacement mutation can survive into adulthood and reproduce. Moreover, when expressed from the c-myc locus, N-myc is similarly regulated and functionally complementary to c-myc in the context of various cellular growth and differentiation processes. Therefore, the myc gene family must have evolved, to a large extent, to facilitate differential patterns of expression.

Original languageEnglish
Pages (from-to)1390-1399
Number of pages10
JournalGenes and Development
Volume14
Issue number11
StatePublished - 1 Jun 2000
Externally publishedYes

Keywords

  • C-myc
  • Gene replacement
  • Knock-in
  • Murine development
  • N-myc
  • Proliferation

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