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Manipulating the Prion Protein Gene Sequence and Expression Levels with CRISPR/Cas9
German Center for Neurodegenerative Diseases (DZNE), Bonn, Germany.
Cologne Excellence Cluster on Cellular Stress Responses in Aging-associated Diseases (CECAD), Medical Faculty, University of Cologne, Cologne, Germany.
Cologne Excellence Cluster on Cellular Stress Responses in Aging-associated Diseases (CECAD), Medical Faculty, University of Cologne, Cologne, Germany.
German Center for Neurodegenerative Diseases (DZNE), Bonn, Germany.
2016 (English)In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 11, no 4, article id e0154604Article in journal (Refereed) Published
Abstract [en]

The mammalian prion protein (PrP, encoded by Prnp) is most infamous for its central role in prion diseases, invariably fatal neurodegenerative diseases affecting humans, food animals, and animals in the wild. However, PrP is also hypothesized to be an important receptor for toxic protein conformers in Alzheimer's disease, and is associated with other clinically relevant processes such as cancer and stroke. Thus, key insights into important clinical areas, as well as into understanding PrP functions in normal physiology, can be obtained from studying transgenic mouse models and cell culture systems. However, the Prnp locus is difficult to manipulate by homologous recombination, making modifications of the endogenous locus rarely attempted. Fortunately in recent years genome engineering technologies, like TALENs or CRISPR/Cas9 (CC9), have brought exceptional new possibilities for manipulating Prnp. Herein, we present our observations made during systematic experiments with the CC9 system targeting the endogenous mouse Prnp locus, to either modify sequences or to boost PrP expression using CC9-based synergistic activation mediators (SAMs). It is our hope that this information will aid and encourage researchers to implement gene-targeting techniques into their research program.

Place, publisher, year, edition, pages
San Francisco, United States: Public Library of Science , 2016. Vol. 11, no 4, article id e0154604
National Category
Medical Biotechnology
Identifiers
URN: urn:nbn:se:liu:diva-146267DOI: 10.1371/journal.pone.0154604ISI: 000375212600047PubMedID: 27128441Scopus ID: 2-s2.0-84966373352OAI: oai:DiVA.org:liu-146267DiVA, id: diva2:1195550
Available from: 2018-04-05 Created: 2018-04-05 Last updated: 2018-04-26Bibliographically approved

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CiteExportLink to record
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