Generation of a homozygous and a heterozygous SNCA gene knockout human-induced pluripotent stem cell line by CRISPR/Cas9 mediated allele-specific tuning of SNCA expression

Aggregation of alpha-synuclein (aSyn) is closely linked to Parkinson's disease, probably due to the loss of physiological functions and/or gain of toxic functions of aggregated aSyn. Significant efforts have been made elucidating the physiological structure and function of aSyn, however, with l...

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Bibliographic Details
Published in:Stem Cell Research
Main Authors: Yanni Schneider, Soeren Turan, Aron Koller, Mandy Krumbiegel, Michaela Farrell, Sonja Plötz, Jürgen Winkler, Wei Xiang
Format: Article
Language:English
Published: Elsevier 2022-12-01
Online Access:http://www.sciencedirect.com/science/article/pii/S1873506122003014
Description
Summary:Aggregation of alpha-synuclein (aSyn) is closely linked to Parkinson's disease, probably due to the loss of physiological functions and/or gain of toxic functions of aggregated aSyn. Significant efforts have been made elucidating the physiological structure and function of aSyn, however, with limited success thus far in human-derived cells, partly because of restricted resources. Here, we developed two human-induced pluripotent stem cell lines using CRISPR/Cas9-mediated allele-specific frame-shift deletion of the aSyn encoding gene SNCA, resulting in homo- and heterozygous SNCA knockout. The generated cell lines are promising cellular tools for studying aSyn dosage-dependent functions and structural alterations in human neural cells.
ISSN:1873-5061