FLP-MEDIATED SITE-SPECIFIC RECOMBINATION IN MICROINJECTED MURINE ZYGOTES

The FLP recombinase of yeast catalyses site-specific recombination bet ween repeated FLP recombinase target (FRT) elements in yeast and in he terologous systems (Escherichia coli, Drosophila, mosquito and culture d mammalian cells). In this report, it is shown that transient FLP rec ombinase expression can recombine and activate an extrachromosomal sil ent reporter gene following coinjection into fertilized one-cell mouse eggs. Furthermore, it is demonstrated that introduction of a FLP-reco mbinase expression vector into transgenic one-cell fertilized mouse eg gs induces a recombination event at a chromosomal FRT target locus. Th e resulting event occured at the one-cell stage and deleted a chromoso mal tandem array of a FRT containing lacZ expression cassette down to one or two copies. These results demonstrate that the FLP recombinase can be utilized to manipulate the genome of transgenic animals and sug gest that FLP recombinase-mediated plasmid-to-chromosome targeting is feasible in microinjected eggs.