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Engineering chromosomes in mice through targeted meiotic recombination (TAMERE)

Abstract

Functional studies of large transcription units, clustered genes and chromosomal loci require the design of novel experimental tools to engineer genomic macro-rearrangements. Here, we present a strategy to produce 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 unequal exchanges. Novel genetic configurations can thus be produced without multiple targeting and selection steps in embryonic stem (ES) cells. A concomitant deletion/duplication event of the Hoxd12 locus shows the potential of this approach. The high frequency of such targeted exchanges in vivo makes TAMERE a powerful genetic tool applicable to research areas in which complex genomic modifications are required.

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Figure 1: The TAMERE strategy.
Figure 2: Detection of TAMERE.
Figure 3: Expression of Hoxd12 in the duplicated/deleted alleles and phenotypes.

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Acknowledgements

We thank M. Friedli, N. Fraudeau and M. Radjkumar for technical assistance and F. Gonzales for his help. We also thank J. Beckers and J. Zákány for mice and other members of the laboratory for their comments and for sharing reagents. This work was supported by funds from the Canton de Genève, the Swiss National Research Fund, the Claraz, Latsis, Cloetta and Jeantet foundations (D.D.) as well as from the Association pour la Recherche sur le Cancer (M.R. and F.C.).

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Hérault, Y., Rassoulzadegan, M., Cuzin, F. et al. Engineering chromosomes in mice through targeted meiotic recombination (TAMERE). Nat Genet 20, 381–384 (1998). https://doi.org/10.1038/3861

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