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Dissecting the role of N-myc in development using a single targeting vector to generate a series of alleles.

The N-myc proto-oncogene is expressed in many organs of the mouse embryo, suggesting that it has multiple functions. A null mutation leads to mid-gestation lethality [1-4], obscuring the later roles of the gene in organogenesis. We have generated a multi-purpose gene alteration by combining the potential for homologous and site-specific recombination in a single targeting vector, and using the selectable marker for neomycin-resistance, neo, to downregulate gene activity. This allowed us to create a series of alleles that led to different levels of N-myc expression. The phenotypes revealed a spectrum of developmental problems. The hypomorphic allele produced can be repaired in situ by Cre-recombinase-mediated DNA excision. We show here for the first time the use of a single targeting vector to generate an allelic series. This, and the possibility of subsequent lineage-specific or conditional allele repair in situ, represent new genome modification strategies that can be used to investigate multiple functions of a single gene.

Pubmed ID: 9635194


  • Nagy A
  • Moens C
  • Ivanyi E
  • Pawling J
  • Gertsenstein M
  • Hadjantonakis AK
  • Pirity M
  • Rossant J


Current biology : CB

Publication Data

May 21, 1998

Associated Grants


Mesh Terms

  • Alleles
  • Animals
  • Base Sequence
  • Congenital Abnormalities
  • DNA Repair
  • DNA, Recombinant
  • Drug Resistance, Microbial
  • Embryonic and Fetal Development
  • Female
  • Gene Expression Regulation, Developmental
  • Gene Targeting
  • Genes, myc
  • Genetic Vectors
  • Heterozygote
  • Homozygote
  • Mice
  • Mice, Transgenic
  • Mutation
  • Neomycin
  • Phenotype
  • Pregnancy