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

Current biology : CB | May 21, 1998

http://www.ncbi.nlm.nih.gov/pubmed/9635194

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.

Pubmed ID: 9635194 RIS Download

Mesh terms: Alleles | Animals | Base Sequence | Congenital Abnormalities | DNA Repair | DNA, Recombinant | Drug Resistance, Microbial | Embryonic and Fetal Development | Female | Gene Expression Regulation, Developmental | Gene Targeting | Genes, myc | Genetic Vectors | Heterozygote | Homozygote | Mice | Mice, Transgenic | Mutation | Neomycin | Phenotype | Pregnancy

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Mouse Genome Informatics (Data, Gene Annotation)

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