Generation of an induced pluripotent stem cell line carrying a biallelic deletion (SCTCi019-A) in GCDH using CRISPR/Cas9

Imke M E Schuurmans; Ka M Wu; Clara D M van Karnebeek; Nael Nadif Kasri; Alejandro Garanto

doi:10.1016/j.scr.2023.103069

Generation of an induced pluripotent stem cell line carrying a biallelic deletion (SCTCi019-A) in GCDH using CRISPR/Cas9

Stem Cell Res. 2023 Jun:69:103069. doi: 10.1016/j.scr.2023.103069. Epub 2023 Mar 15.

Authors

Imke M E Schuurmans¹, Ka M Wu², Clara D M van Karnebeek³, Nael Nadif Kasri², Alejandro Garanto⁴

Affiliations

¹ Department of Pediatrics, Radboud University Medical Center, Nijmegen, The Netherlands; Radboud Institute for Molecular Life Sciences, Radboud University Medical Center, Nijmegen, The Netherlands; Amalia Children's Hospital, Radboud University Medical Center, Nijmegen, The Netherlands; Departments of Pediatrics and Human Genetics, Emma Center for Personalized Medicine, Amsterdam University Medical Centers, University of Amsterdam, The Netherlands.
² Department of Human Genetics, Radboud University Medical Center, Nijmegen, The Netherlands; Donders Institute for Brain, Cognition and Behaviour, Radboud University Medical Center, Nijmegen, The Netherlands.
³ Departments of Pediatrics and Human Genetics, Emma Center for Personalized Medicine, Amsterdam University Medical Centers, University of Amsterdam, The Netherlands; United for Metabolic Diseases, Amsterdam, The Netherlands; Amsterdam Gastroenterology Endocrinology Metabolism, Amsterdam, The Netherlands.
⁴ Department of Pediatrics, Radboud University Medical Center, Nijmegen, The Netherlands; Radboud Institute for Molecular Life Sciences, Radboud University Medical Center, Nijmegen, The Netherlands; Amalia Children's Hospital, Radboud University Medical Center, Nijmegen, The Netherlands; Department of Human Genetics, Radboud University Medical Center, Nijmegen, The Netherlands. Electronic address: alex.garanto@radboudumc.nl.

PMID: 36947993
DOI: 10.1016/j.scr.2023.103069

Abstract

GCDH encodes for the enzyme catalyzing the sixth step of the lysine catabolism pathway. Biallelic pathogenic variants in GCDH have been associated with glutaric aciduria type 1 (GA1). In this study CRISPR/Cas9 technology was used to create an isogenic GCDH knock-out human iPSC line. One clone with a biallelic deletion (SCTCi019-A) in GCDH was obtained and fully characterized, revealing a normal karyotype, no off-targets detected and expression of pluripotency markers. This iPSC line can contribute to gain insights in the molecular mechanism of disease.

Publication types

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

MeSH terms

Amino Acid Metabolism, Inborn Errors* / genetics
Brain Diseases, Metabolic* / genetics
Brain Diseases, Metabolic* / metabolism
CRISPR-Cas Systems / genetics
Humans
Induced Pluripotent Stem Cells* / metabolism

Supplementary concepts

Glutaric Acidemia I