Isogenic human SNCA gene dosage induced pluripotent stem cells to model Parkinson's disease
Faria Zafar1, Vasavi Nallur Srinivasaraghavan1, Max Yang Chen1
1Stanford University School of Medicine, Department of Pathology, Stanford, CA, 94305, U.S.A.
Abstract:
Alpha-synuclein overexpression and aggregation are critical factors in the pathogenesis of Parkinson's disease (PD). Clinical cases with alpha-synuclein (SNCA) multiplications or deletions indicate that gene expression levels are essential for neurodegeneration and neurodevelopment. Here, we developed an isogenic SNCA gene dosage model using CRISPR/Cas9 gene editing to introduce frameshift mutations into exon 2 of the SNCA coding region in human induced pluripotent stem cells (iPSCs) from a patient with an SNCA triplication. We derived and characterized clones with different frameshift mutations. This isogenic SNCA gene dosage panel will address the physiological and detrimental effects of varying alpha-synuclein expression levels.
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