Isogenic human SNCA gene dosage induced pluripotent stem cells to model Parkinson’s disease

[摘要] 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.

[学科分类] 生理学

[关键词] Clustered regularly interspaced short palindromic repeat;CRISPR;Cas9;Alpha-synuclein;SNCA;Gene regulation;Gene editing;Parkinson’s disease;Developmental delay;Autism spectrum disorder