Universität zu Köln

Kaczmarczyk, Lech ORCID: 0000-0003-2747-3134, Mende, Ylva, Zevnik, Branko ORCID: 0000-0001-7845-9522 and Jackson, Walker S. (2016). Manipulating the Prion Protein Gene Sequence and Expression Levels with CRISPR/Cas9. PLoS One, 11 (4). SAN FRANCISCO: PUBLIC LIBRARY SCIENCE. ISSN 1932-6203

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Abstract

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.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Kaczmarczyk, Lech UNSPECIFIED orcid.org/0000-0003-2747-3134 UNSPECIFIED Mende, Ylva UNSPECIFIED UNSPECIFIED UNSPECIFIED Zevnik, Branko UNSPECIFIED orcid.org/0000-0001-7845-9522 UNSPECIFIED Jackson, Walker S. UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-278222
DOI:	10.1371/journal.pone.0154604
Journal or Publication Title:	PLoS One
Volume:	11
Number:	4
Date:	2016
Publisher:	PUBLIC LIBRARY SCIENCE
Place of Publication:	SAN FRANCISCO
ISSN:	1932-6203
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language TRANSMISSIBLE SPONGIFORM ENCEPHALOPATHY; ONE-STEP GENERATION; SYNAPTIC PLASTICITY; TRANSGENIC MICE; HOMOLOGOUS RECOMBINATION; ALZHEIMERS-DISEASE; PRP; SCRAPIE; CRISPR-CAS9; CELLS Multiple languages Multidisciplinary Sciences Multiple languages
Refereed:	Yes
URI:	http://kups.ub.uni-koeln.de/id/eprint/27822