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Originally published as Genetics Published Articles Ahead of Print on August 30, 2008.
Genetics, Vol. 180, 51-59, September 2008, Copyright © 2008
doi:10.1534/genetics.108.092312
Inducing Segmental Aneuploid Mosaicism in the Mouse Through Targeted Asymmetric Sister Chromatid Event of Recombination
Arnaud Duchon*,
,
Vanessa Besson*,,
Patricia Lopes Pereira*,,
Laetitia Magnol*, and
Yann Hérault*,,
,1
* Université d'Orléans, UMR6218, Molecular Immunology and Embryology, 45071 Orléans Cedex 2, France, Centre National de la Recherche Scientifique, UMR6218, Immunologie and Molecular Embryology, 45071 Orléans Cedex 2, France and Centre National de la Recherche Scientifique, UPS44, Transgenese, Archivage Animaux Modèles, Institut de Transgenose, 45071 Orléans Cedex 2, France
1 Corresponding author: CNRS, Institut de Transgénose 3B rue de la Férollerie, 45071 Orléans Cedex 2 France.
E-mail: herault{at}cnrs-orleans.fr
Loss or gain of whole chromosomes, or parts of chromosomes, is found in various pathological conditions, such as cancer and aneuploidy, and results from the missegregation of chromosomes during cellular division or abnormal mitotic recombination. We introduce a novel strategy for determining the consequences of segmental aneuploid mosaicism, called targeted asymmetric sister chromatin event of recombination (TASCER). We took advantage of the Cre/loxP system, used extensively in embryonic stem cells for generating deletions and duplications of regions of interest, to induce recombination during the G2 phase. Using two loxP sites in a Cis configuration, we generated in vivo cells harboring microdeletions and microduplications for regions of interest covering up to 2.2 Mb. Using this approach in the mouse provides insight into the consequences of segmental aneuploidy for homologous regions of the human chromosome 21 on cell survival. Furthermore, TASCER shows that Cre-induced recombination is more efficient after DNA replication in vivo and provides an opportunity to evaluate, through genetic mosaics, the outcome of copy number variation and segmental aneuploidy in the mouse.
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Genetics 2008 180: NP.
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