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

Curr Biol. 1998 May 21;8(11):661-4. doi: 10.1016/s0960-9822(98)70254-4.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

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


  • DNA, Recombinant
  • Neomycin