ALTERATION OF CAENORHABDITIS-ELEGANS GENE-EXPRESSION BY TARGETED TRANSFORMATION

We have produced strains carrying a synthetic fusion of parts of two v itellogenin genes, vit-2 and vit-6, integrated into the Caenorhabditis elegans genome. In most of the 63 transformant strains, the plasmid s equences are integrated at random locations in the genome. However, in two strains the transgene integrated by homologous recombination into the endogenous vit-2 gene. In both cases the reciprocal exchange betw een the chromosome and the injected circular plasmid containing a prom oter deletion led to switching of the plasmid-borne promoter and the e ndogenous promoter, with a reduction in vit-2 expression. Thus in nema todes, transforming DNA can integrate by homologous recombination to r esult in partial inactivation of the chromosomal locus. The simplicity of the event and its reasonably high frequency suggest that gene targ eting by homologous recombination should be considered as a method for directed inactivation of C. elegans genes.