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

Stem cell research

article

Faria Zafar¹  Vasavi Nallur Srinivasaraghavan¹  Max Yang Chen¹  C. Alejandra Morato Torres¹  Birgitt Schüle¹ 

[1] Stanford University School of Medicine, Department of Pathology

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;   

DOI  :  10.1016/j.scr.2022.102733

学科分类：生理学

来源: Academic Press

【 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.

【 授权许可】

CC BY|CC BY-NC-ND