Generation of induced pluripotent stem cell (iPSC) lines carrying a heterozygous (UKWMPi002-A-1) and null mutant knockout (UKWMPi002-A-2) of Cadherin 13 associated with neurodevelopmental disorders using CRISPR/Cas9

Maria Rosaria Vitale; Johanna Eva Maria Zöller; Charline Jansch; Anna Janz; Frank Edenhofer; Eva Klopocki; Daniel van den Hove; Tim Vanmierlo; Olga Rivero; Nael Nadif Kasri; Georg Christoph Ziegler; Klaus-Peter Lesch

doi:10.1016/j.scr.2021.102169

Generation of induced pluripotent stem cell (iPSC) lines carrying a heterozygous (UKWMPi002-A-1) and null mutant knockout (UKWMPi002-A-2) of Cadherin 13 associated with neurodevelopmental disorders using CRISPR/Cas9

Stem Cell Res. 2021 Mar:51:102169. doi: 10.1016/j.scr.2021.102169. Epub 2021 Jan 11.

Affiliations

¹ Division of Molecular Psychiatry, Center of Mental Health, University Hospital Würzburg, Germany; Laboratory of Psychiatric Neurobiology, Institute of Molecular Medicine, I.M Sechenov First Moscow State Medical University, Moscow, Russia. Electronic address: [email protected].
² Division of Molecular Psychiatry, Center of Mental Health, University Hospital Würzburg, Germany; Department of Psychiatry and Neuropsychology, School for Mental Health and Neuroscience (MHeNs), Maastricht University, Maastricht, The Netherlands.
³ Division of Molecular Psychiatry, Center of Mental Health, University Hospital Würzburg, Germany.
⁴ Comprehensive Heart Failure Center (CHFC) and Department of Internal Medicine I, University Hospital Würzburg, Germany.
⁵ Department of Genomics, Stem Cell Biology and Regenerative Medicine, Institute of Molecular Biology & CMBI, Leopold-Franzens-University Innsbruck, Innsbruck, Austria.
⁶ Institute of Human Genetics, Biocentre, University of Würzburg, Germany.
⁷ Department of Psychiatry and Neuropsychology, School for Mental Health and Neuroscience (MHeNs), Maastricht University, Maastricht, The Netherlands; Neuro-immune Connect and Repair Lab, Biomedical Research Institute, Hasselt University, Belgium.
⁸ Department of Cognitive Neuroscience, Donders Institute for Brain, Cognition, and Behaviour, Radboud University Medical Center, Nijmegen, The Netherlands; Department of Human Genetics, Donders Institute for Brain, Cognition, and Behaviour, Radboud University Medical Center, Nijmegen, The Netherlands.
⁹ Division of Molecular Psychiatry, Center of Mental Health, University Hospital Würzburg, Germany; Department of Psychiatry, Psychosomatics and Psychotherapy, Center of Mental Health, University Hospital Würzburg, Germany.
¹⁰ Division of Molecular Psychiatry, Center of Mental Health, University Hospital Würzburg, Germany; Laboratory of Psychiatric Neurobiology, Institute of Molecular Medicine, I.M Sechenov First Moscow State Medical University, Moscow, Russia; Department of Psychiatry and Neuropsychology, School for Mental Health and Neuroscience (MHeNs), Maastricht University, Maastricht, The Netherlands. Electronic address: [email protected].

PMID: 33486346
DOI: 10.1016/j.scr.2021.102169

Abstract

Fibroblasts isolated from a skin biopsy of a healthy 46-year-old female were infected with Sendai virus containing the Yamanaka factors to produce transgene-free human induced pluripotent stem cells (iPSCs). CRISPR/Cas9 was used to generate isogenic cell lines with a gene dose-dependent deficiency of CDH13, a risk gene associated with neurodevelopmental and psychiatric disorders. Thereby, a heterozygous CDH13 knockout (CDH13^+/-) and a CDH13 null mutant (CDH13^-/-) iPSC line was obtained. All three lines showed expression of pluripotency-associated markers, the ability to differentiate into cells of the three germ layers in vitro, and a normal female karyotype.

Publication types

Case Reports
Research Support, Non-U.S. Gov't

MeSH terms

CRISPR-Cas Systems
Cadherins
Female
Heterozygote
Humans
Induced Pluripotent Stem Cells*
Middle Aged
Neurodevelopmental Disorders* / genetics

Substances

Cadherins
H-cadherin