title: Efficient and rapid generation of large genomic variants in rats and mice using CRISMERE.
abstract: Modelling Down syndrome (DS) in mouse has been crucial for the understanding of the disease and the evaluation of therapeutic targets. Nevertheless, the modelling so far has been limited to the mouse and, even in this model, generating duplication of genomic regions has been labour intensive and time consuming. We developed the CRISpr MEdiated REarrangement (CRISMERE) strategy, which takes advantage of the CRISPR/Cas9 system, to generate most of the desired rearrangements from a single experiment at much lower expenses and in less than 9 months. Deletions, duplications, and inversions of genomic regions as large as 24.4 Mb in rat and mouse founders were observed and germ line transmission was confirmed for fragment as large as 3.6 Mb. Interestingly we have been able to recover duplicated regions from founders in which we only detected deletions. CRISMERE is even more powerful than anticipated it allows the scientific community to manipulate the rodent and probably other genomes in a fast and efficient manner which was not possible before.
authors.affiliation: PHENOMIN, Institut Clinique de la Souris (ICS), CNRS, INSERM, University of Strasbourg, 1 rue Laurent Fries, F-67404 Illkirch-Graffenstaden, France.
authors.forename: Marie-Christine
authors.initials: MC
authors.lastname: Birling
authors.affiliation: PHENOMIN, Institut Clinique de la Souris (ICS), CNRS, INSERM, University of Strasbourg, 1 rue Laurent Fries, F-67404 Illkirch-Graffenstaden, France.
authors.forename: Laurence
authors.initials: L
authors.lastname: Schaeffer
authors.affiliation: PHENOMIN, Institut Clinique de la Souris (ICS), CNRS, INSERM, University of Strasbourg, 1 rue Laurent Fries, F-67404 Illkirch-Graffenstaden, France.
authors.forename: Philippe
authors.initials: P
authors.lastname: André
authors.affiliation: PHENOMIN, Institut Clinique de la Souris (ICS), CNRS, INSERM, University of Strasbourg, 1 rue Laurent Fries, F-67404 Illkirch-Graffenstaden, France.
authors.forename: Loic
authors.initials: L
authors.lastname: Lindner
authors.affiliation: PHENOMIN, Institut Clinique de la Souris (ICS), CNRS, INSERM, University of Strasbourg, 1 rue Laurent Fries, F-67404 Illkirch-Graffenstaden, France.
authors.forename: Damien
authors.initials: D
authors.lastname: Maréchal
authors.affiliation: PHENOMIN, Institut Clinique de la Souris (ICS), CNRS, INSERM, University of Strasbourg, 1 rue Laurent Fries, F-67404 Illkirch-Graffenstaden, France.
authors.forename: Abdel
authors.initials: A
authors.lastname: Ayadi
authors.affiliation: PHENOMIN, Institut Clinique de la Souris (ICS), CNRS, INSERM, University of Strasbourg, 1 rue Laurent Fries, F-67404 Illkirch-Graffenstaden, France.
authors.forename: Tania
authors.initials: T
authors.lastname: Sorg
authors.affiliation: PHENOMIN, Institut Clinique de la Souris (ICS), CNRS, INSERM, University of Strasbourg, 1 rue Laurent Fries, F-67404 Illkirch-Graffenstaden, France.
authors.forename: Guillaume
authors.initials: G
authors.lastname: Pavlovic
authors.affiliation: PHENOMIN, Institut Clinique de la Souris (ICS), CNRS, INSERM, University of Strasbourg, 1 rue Laurent Fries, F-67404 Illkirch-Graffenstaden, France.|Institut de Génétique et de Biologie Moléculaire et Cellulaire, Illkirch, France.|Centre National de la Recherche Scientifique, UMR7104, Illkirch, France.|Institut National de la Santé et de la Recherche Médicale, U964, Illkirch, France.|Université de Strasbourg, Illkirch, France.
authors.forename: Yann
authors.initials: Y
authors.lastname: Hérault
mesh_terms: D000818:Animals; D030801:Animals, Genetically Modified; D000072669:Gene Editing / Q000379:methods*; D015321:Gene Rearrangement; D051379:Mice; D051381:Rats; D013997:Time Factors