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

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.

DOI: 10.1016/S0960-9822(98)70254-4

Extracted Key Phrases

3 Figures and Tables

050100'99'01'03'05'07'09'11'13'15'17
Citations per Year

752 Citations

Semantic Scholar estimates that this publication has 752 citations based on the available data.

See our FAQ for additional information.

Cite this paper

@article{Nagy1998DissectingTR, title={Dissecting the role of N-myc in development using a single targeting vector to generate a series of alleles}, author={Attila Cs Nagy and C H Moens and Enik{\"{o} Iv{\'a}nyi and Judy Pawling and Marina Gertsenstein and A-K. Hadjantonakis and Melinda Katalin Pirity and Janet Rossant}, journal={Current Biology}, year={1998}, volume={8}, pages={661-666} }