title: Deletions, Inversions, Duplications: Engineering of Structural Variants using CRISPR/Cas in Mice.
abstract: Structural variations (SVs) contribute to the variability of our genome and are often associated with disease. Their study in model systems was hampered until now by labor-intensive genetic targeting procedures and multiple mouse crossing steps. Here we present the use of CRISPR/Cas for the fast (10 weeks) and efficient generation of SVs in mice. We specifically produced deletions, inversions, and also duplications at six different genomic loci ranging from 1.1 kb to 1.6 Mb with efficiencies up to 42%. After PCR-based selection, clones were successfully used to create mice via aggregation. To test the practicability of the method, we reproduced a human 500 kb disease-associated deletion and were able to recapitulate the human phenotype in mice. Furthermore, we evaluated the regulatory potential of a large genomic interval by deleting a 1.5 Mb fragment. The method presented permits rapid in vivo modeling of genomic rearrangements.
authors: Max Planck Institute for Molecular Genetics, 14195 Berlin, Germany.
authors: Katerina
authors: K
authors: Kraft
authors: Max Planck Institute for Molecular Genetics, 14195 Berlin, Germany; Institute for Medical and Human Genetics, Charité Universitätsmedizin Berlin, 13353 Berlin, Germany.
authors: Sinje
authors: S
authors: Geuer
authors: Max Planck Institute for Molecular Genetics, 14195 Berlin, Germany; Institute for Medical and Human Genetics, Charité Universitätsmedizin Berlin, 13353 Berlin, Germany.
authors: Anja J
authors: AJ
authors: Will
authors: Institute for Medical and Human Genetics, Charité Universitätsmedizin Berlin, 13353 Berlin, Germany.
authors: Wing Lee
authors: WL
authors: Chan
authors: Max Planck Institute for Molecular Genetics, 14195 Berlin, Germany.
authors: Christina
authors: C
authors: Paliou
authors: Max Planck Institute for Molecular Genetics, 14195 Berlin, Germany.
authors: Marina
authors: M
authors: Borschiwer
authors: Max Planck Institute for Molecular Genetics, 14195 Berlin, Germany.
authors: Izabela
authors: I
authors: Harabula
authors: Max Planck Institute for Molecular Genetics, 14195 Berlin, Germany.
authors: Lars
authors: L
authors: Wittler
authors: Max Planck Institute for Molecular Genetics, 14195 Berlin, Germany; Institute for Medical and Human Genetics, Charité Universitätsmedizin Berlin, 13353 Berlin, Germany.
authors: Martin
authors: M
authors: Franke
authors: Max Planck Institute for Molecular Genetics, 14195 Berlin, Germany; Berlin-Brandenburg Center for Regenerative Therapies (BCRT), Charité Universitätsmedizin Berlin, 13353 Berlin, Germany.
authors: Daniel M
authors: DM
authors: Ibrahim
authors: Max Planck Institute for Molecular Genetics, 14195 Berlin, Germany; Institute for Medical and Human Genetics, Charité Universitätsmedizin Berlin, 13353 Berlin, Germany; Berlin-Brandenburg Center for Regenerative Therapies (BCRT), Charité Universitätsmedizin Berlin, 13353 Berlin, Germany.
authors: Bjørt K
authors: BK
authors: Kragesteen
authors: Max Planck Institute for Molecular Genetics, 14195 Berlin, Germany; Institute for Medical and Human Genetics, Charité Universitätsmedizin Berlin, 13353 Berlin, Germany; Berlin-Brandenburg Center for Regenerative Therapies (BCRT), Charité Universitätsmedizin Berlin, 13353 Berlin, Germany; Berlin-Brandenburg School for Regenerative Therapies (BSRT), Charité Universitätsmedizin Berlin, 13353 Berlin, Germany.
authors: Malte
authors: M
authors: Spielmann
authors: Max Planck Institute for Molecular Genetics, 14195 Berlin, Germany; Institute for Medical and Human Genetics, Charité Universitätsmedizin Berlin, 13353 Berlin, Germany; Berlin-Brandenburg Center for Regenerative Therapies (BCRT), Charité Universitätsmedizin Berlin, 13353 Berlin, Germany; Berlin-Brandenburg School for Regenerative Therapies (BSRT), Charité Universitätsmedizin Berlin, 13353 Berlin, Germany.
authors: Stefan
authors: S
authors: Mundlos
authors: Max Planck Institute for Molecular Genetics, 14195 Berlin, Germany. Electronic address: lupianez@molgen.mpg.de.
authors: Darío G
authors: DG
authors: Lupiáñez
authors: Max Planck Institute for Molecular Genetics, 14195 Berlin, Germany. Electronic address: andrey@molgen.mpg.de.
authors: Guillaume
authors: G
authors: Andrey