Generation of a human induced pluripotent stem cell line (UQi001-A-1) edited with the CRISPR-Cas9 system to carry the heterozygous TARDBP c.1144G > A (p.A382T) missense mutation

Timothy J Tracey; Leanne Jiang; Melinder K Gill; Samara N Ranie; Dmitry A Ovchinnikov; Ernst J Wolvetang; Shyuan T Ngo

doi:10.1016/j.scr.2023.103137

Generation of a human induced pluripotent stem cell line (UQi001-A-1) edited with the CRISPR-Cas9 system to carry the heterozygous TARDBP c.1144G > A (p.A382T) missense mutation

Stem Cell Res. 2023 Aug:70:103137. doi: 10.1016/j.scr.2023.103137. Epub 2023 Jun 7.

Authors

Timothy J Tracey¹, Leanne Jiang², Melinder K Gill³, Samara N Ranie⁴, Dmitry A Ovchinnikov⁵, Ernst J Wolvetang⁴, Shyuan T Ngo⁶

Affiliations

¹ Australian Institute for Bioengineering and Nanotechnology, The University of Queensland, Brisbane, Australia. Electronic address: t.tracey@uq.edu.au.
² Australian Institute for Bioengineering and Nanotechnology, The University of Queensland, Brisbane, Australia; Perron Institute for Neurological and Translational Science, Perth, Australia; School of Biological Science, University of Western Australia, Perth, Australia.
³ School of Biomedical Sciences, The University of Queensland, Brisbane, Australia.
⁴ Australian Institute for Bioengineering and Nanotechnology, The University of Queensland, Brisbane, Australia.
⁵ Australian Institute for Bioengineering and Nanotechnology, The University of Queensland, Brisbane, Australia; Florey Institute for Neuroscience and Mental Health, University of Melbourne, Melbourne, Australia.
⁶ Australian Institute for Bioengineering and Nanotechnology, The University of Queensland, Brisbane, Australia. Electronic address: s.ngo@uq.edu.au.

PMID: 37315423
DOI: 10.1016/j.scr.2023.103137

Abstract

Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease in which the TDP-43 protein is believed to play a central role in disease pathophysiology. Using the CRISPR-Cas9 system, we introduced the heterozygous c.1144G > A (p.A382T) missense mutation in exon 6 of the TARDBP gene into an iPSC line derived from a healthy individual. These edited iPSCs displayed normal cellular morphology, expressed major pluripotency markers, were capable of tri-lineage differentiation, and possessed a normal karyotype.

Publication types

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

MeSH terms

Amyotrophic Lateral Sclerosis* / genetics
CRISPR-Cas Systems / genetics
DNA-Binding Proteins / genetics
Humans
Induced Pluripotent Stem Cells* / cytology
Mutation
Mutation, Missense
Neurodegenerative Diseases* / genetics

Substances

DNA-Binding Proteins
TARDBP protein, human