First Author | Nagy A | Year | 1998 |
Journal | Curr Biol | Volume | 8 |
Issue | 11 | Pages | 661-4 |
PubMed ID | 9635194 | Mgi Jnum | J:67930 |
Mgi Id | MGI:1931705 | Doi | 10.1016/s0960-9822(98)70254-4 |
Citation | Nagy A, et al. (1998) Dissecting the role of N-myc in development using a single targeting vector to generate a series of alleles. Curr Biol 8(11):661-4 |
abstractText | 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. |