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

A. Nagy, C. Moens, E. Ivanyi, J. Pawling, M. Gertsenstein, A. K. Hadjantonakis, M. Pirity, J. Rossant

Research output: Contribution to journalArticle

152 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)661-664
Number of pages4
JournalCurrent Biology
Volume8
Issue number11
Publication statusPublished - May 21 1998

Fingerprint

Genes
Alleles
alleles
genes
site-specific recombination
proto-oncogenes
myc Genes
Neomycin
Organogenesis
neomycin
organogenesis
Genetic Recombination
embryo (animal)
Down-Regulation
Embryonic Structures
pregnancy
Genome
Phenotype
phenotype
Repair

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)

Cite this

Nagy, A., Moens, C., Ivanyi, E., Pawling, J., Gertsenstein, M., Hadjantonakis, A. K., ... Rossant, J. (1998). Dissecting the role of N-myc in development using a single targeting vector to generate a series of alleles. Current Biology, 8(11), 661-664.

Dissecting the role of N-myc in development using a single targeting vector to generate a series of alleles. / Nagy, A.; Moens, C.; Ivanyi, E.; Pawling, J.; Gertsenstein, M.; Hadjantonakis, A. K.; Pirity, M.; Rossant, J.

In: Current Biology, Vol. 8, No. 11, 21.05.1998, p. 661-664.

Research output: Contribution to journalArticle

Nagy, A, Moens, C, Ivanyi, E, Pawling, J, Gertsenstein, M, Hadjantonakis, AK, Pirity, M & Rossant, J 1998, 'Dissecting the role of N-myc in development using a single targeting vector to generate a series of alleles', Current Biology, vol. 8, no. 11, pp. 661-664.
Nagy A, Moens C, Ivanyi E, Pawling J, Gertsenstein M, Hadjantonakis AK et al. Dissecting the role of N-myc in development using a single targeting vector to generate a series of alleles. Current Biology. 1998 May 21;8(11):661-664.
Nagy, A. ; Moens, C. ; Ivanyi, E. ; Pawling, J. ; Gertsenstein, M. ; Hadjantonakis, A. K. ; Pirity, M. ; Rossant, J. / Dissecting the role of N-myc in development using a single targeting vector to generate a series of alleles. In: Current Biology. 1998 ; Vol. 8, No. 11. pp. 661-664.
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