ENGINEERING CHROMOSOMES IN MICE THROUGH TARGETED MEIOTIC RECOMBINATION (TAMERE)

Functional studies of large transcription units, clustered genes and c hromosomal loci require the design of novel experimental toots to engi neer genomic macro-rearrangements. Here, we present a strategy to prod uce deficiencies or duplications by crossing mice carrying loxP sites in homologous loci. This trans-allelic targeted meiotic recombination (TAMERE) protocol allows for the combination of various alleles within a particular locus as well as for generation of interchromosomal uneq ual exchanges. Novel genetic configurations can thus be produced witho ut multiple targeting and selection steps in embryonic stem (ES) cells . A concomitant deletion/duplication event of the Hoxd12 locus shows t he potential of this approach. The high frequency of such targeted exc hanges in vivo makes TAMERE a powerful genetic tool applicable to rese arch areas in which complex genomic modifications are required.