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

Carol X.-Q. Chen; Zhipeng You; Narges Abdian; Julien Sirois; Irina Shlaifer; Mahdieh Tabatabaei; Marie-Noëlle Boivin; Lydiane Gaborieau; Jason Karamchandani; Lenore K. Beitel; Edward A. Fon; Thomas M. Durcan

Stem Cell Research (Jul 2022)

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

Carol X.-Q. Chen,
Zhipeng You,
Narges Abdian,
Julien Sirois,
Irina Shlaifer,
Mahdieh Tabatabaei,
Marie-Noëlle Boivin,
Lydiane Gaborieau,
Jason Karamchandani,
Lenore K. Beitel,
Edward A. Fon,
Thomas M. Durcan

Affiliations

Carol X.-Q. Chen: The Neuro’s Early Drug Discovery Unit (EDDU), McGill University, 3801 University Street, Montreal, QC H3A 2B4, Canada
Zhipeng You: The Neuro’s Early Drug Discovery Unit (EDDU), McGill University, 3801 University Street, Montreal, QC H3A 2B4, Canada
Narges Abdian: The Neuro’s Early Drug Discovery Unit (EDDU), McGill University, 3801 University Street, Montreal, QC H3A 2B4, Canada
Julien Sirois: The Neuro’s Early Drug Discovery Unit (EDDU), McGill University, 3801 University Street, Montreal, QC H3A 2B4, Canada
Irina Shlaifer: The Neuro’s Early Drug Discovery Unit (EDDU), McGill University, 3801 University Street, Montreal, QC H3A 2B4, Canada
Mahdieh Tabatabaei: C-BIG Repository (C-BIG), Montreal Neurological Institute-Hospital, McGill University, Montreal, QC H3A 2B4, Canada
Marie-Noëlle Boivin: C-BIG Repository (C-BIG), Montreal Neurological Institute-Hospital, McGill University, Montreal, QC H3A 2B4, Canada
Lydiane Gaborieau: C-BIG Repository (C-BIG), Montreal Neurological Institute-Hospital, McGill University, Montreal, QC H3A 2B4, Canada
Jason Karamchandani: C-BIG Repository (C-BIG), Montreal Neurological Institute-Hospital, McGill University, Montreal, QC H3A 2B4, Canada
Lenore K. Beitel: The Neuro’s Early Drug Discovery Unit (EDDU), McGill University, 3801 University Street, Montreal, QC H3A 2B4, Canada
Edward A. Fon: McGill Parkinson Program and Neurodegenerative Diseases Group, Montreal Neurological Institute, Department of Neurology and Neurosurgery, Montreal, QC H3A 2B4, Canada
Thomas M. Durcan: The Neuro’s Early Drug Discovery Unit (EDDU), McGill University, 3801 University Street, Montreal, QC H3A 2B4, Canada; Corresponding author.

Journal volume & issue: Vol. 62
p. 102806

Abstract

Read online

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.

Published in Stem Cell Research

ISSN: 1873-5061 (Print); 1876-7753 (Online)
Publisher: Elsevier
Country of publisher: Netherlands
LCC subjects: Science: Biology (General)
Website: https://www.journals.elsevier.com/stem-cell-research

About the journal