English
 
User Manual Privacy Policy Disclaimer Contact us
  Advanced SearchBrowse

Item

ITEM ACTIONSEXPORT

Released

Journal Article

Deletions, Inversions, Duplications: Engineering of Structural Variants using CRISPR/Cas in Mice

MPS-Authors
/persons/resource/persons73905

Kraft,  K.
Research Group Development & Disease (Head: Stefan Mundlos), Max Planck Institute for Molecular Genetics, Max Planck Society;

Geuer,  S.
Max Planck Society;

Will,  A. J.
Max Planck Society;

Paliou,  C.
Max Planck Society;

Borschiwer,  M.
Max Planck Society;

Harabula,  I.
Max Planck Society;

/persons/resource/persons50647

Wittler,  L.
Dept. of Developmental Genetics (Head: Bernhard G. Herrmann), Max Planck Institute for Molecular Genetics, Max Planck Society;

/persons/resource/persons73895

Franke,  M.
Research Group Development & Disease (Head: Stefan Mundlos), Max Planck Institute for Molecular Genetics, Max Planck Society;

/persons/resource/persons73903

Ibrahim,  D.
Research Group Development & Disease (Head: Stefan Mundlos), Max Planck Institute for Molecular Genetics, Max Planck Society;

Kragesteen,  B. K.
Max Planck Society;

/persons/resource/persons50565

Spielmann,  M.
Research Group Development & Disease (Head: Stefan Mundlos), Max Planck Institute for Molecular Genetics, Max Planck Society;

/persons/resource/persons50437

Mundlos,  S.
Research Group Development & Disease (Head: Stefan Mundlos), Max Planck Institute for Molecular Genetics, Max Planck Society;

Lupianez,  D. G.
Max Planck Society;

Andrey,  G.
Max Planck Society;

External Ressource
Fulltext (public)

Kraft.pdf
(Publisher version), 2MB

Supplementary Material (public)
There is no public supplementary material available
Citation

Kraft, K., Geuer, S., Will, A. J., Chan, W. L., Paliou, C., Borschiwer, M., et al. (2015). Deletions, Inversions, Duplications: Engineering of Structural Variants using CRISPR/Cas in Mice. Cell Reports, 10(5), 833-839. doi:10.1016/j.celrep.2015.01.016.


Cite as: http://hdl.handle.net/11858/00-001M-0000-0025-78F1-2
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.