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Curr Biol. 1998 May 21;8(11):661-4.

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

Author information

1
Samuel Lunenfeld Research Institute, Mount Sinai Hospital, Toronto, Canada. nagy@mshri.on.ca

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.

PMID:
9635194
DOI:
10.1016/s0960-9822(98)70254-4
[Indexed for MEDLINE]
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