Generation of homozygous PRKN, PINK1 and double PINK1/PRKN knockout cell lines from healthy induced pluripotent stem cells using CRISPR/Cas9 editing

被引:11
作者
Chen, Carol X. -Q. [1 ]
You, Zhipeng [1 ]
Abdian, Narges [1 ]
Sirois, Julien [1 ]
Shlaifer, Irina [1 ]
Tabatabaei, Mahdieh [2 ]
Boivin, Marie-Noelle [2 ]
Gaborieau, Lydiane [2 ]
Karamchandani, Jason [2 ]
Beitel, Lenore K. [1 ]
Fon, Edward A. [3 ,4 ]
Durcan, Thomas M. [1 ]
机构
[1] McGill Univ, Neuros Early Drug Discovery Unit EDDU, 3801 Univ St, Montreal, PQ H3A 2B4, Canada
[2] McGill Univ, C BIG Repository C BIG, Montreal Neurol Inst, Montreal, PQ H3A 2B4, Canada
[3] Montreal Neurol Inst, Dept Neurol & Neurosurg, McGill Parkinson Program, Montreal, PQ H3A 2B4, Canada
[4] Montreal Neurol Inst, Dept Neurol & Neurosurg, Neurodegenerat Dis Grp, Montreal, PQ H3A 2B4, Canada
关键词
D O I
10.1016/j.scr.2022.102806
中图分类号
Q813 [细胞工程];
学科分类号
摘要
Autosomal recessive mutations in either PRKN or PINK1 are associated with early-onset Parkinson's disease. The corresponding proteins, PRKN, an E3 ubiquitin ligase, and the mitochondrial serine/threonine-protein kinase PINK1 play a role in mitochondrial quality control. Using CRISPR/CAS9 technology we generated three human iPSC lines from the well characterized AIW002-02 control line. These isogenic iPSCs contain homozygous knockouts of PRKN (PRKN-KO, CBIGi001-A-1), PINK1 (PINK1-KO, CBIGi001-A-2) or both PINK1 and PRKN (PINK1-KO/PRKN-KO, CBIGi001-A-3). The knockout lines display normal karyotypes, express pluripotency markers and upon differentiation into relevant brain cells or midbrain organoids may be valuable tools to model Parkinson's disease.
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页数:7
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