Generation of a human induced pluripotent stem cell line via CRISPR-Cas9 mediated integration of a site-specific heterozygous mutation in CHMP2B

Yu Zhang; Benjamin Schmid; Troels T Nielsen; Jørgen E Nielsen; Christian Clausen; Poul Hyttel; Bjørn Holst; Kristine K Freude

doi:10.1016/j.scr.2016.06.004

Generation of a human induced pluripotent stem cell line via CRISPR-Cas9 mediated integration of a site-specific heterozygous mutation in CHMP2B

Stem Cell Res. 2016 Jul;17(1):148-150. doi: 10.1016/j.scr.2016.06.004. Epub 2016 Jun 16.

Authors

Yu Zhang¹, Benjamin Schmid², Troels T Nielsen³, Jørgen E Nielsen³, Christian Clausen², Poul Hyttel⁴, Bjørn Holst², Kristine K Freude⁵

Affiliations

¹ Stem Cells and Embryology Group, Department of Veterinary Clinical and Animal Sciences, Faculty of Health and Medical Sciences, University of Copenhagen, Denmark. Electronic address: yu.zhang@sund.ku.dk.
² Bioneer A/S, Hørsholm, Denmark.
³ Neurogenetics Clinic & Research Lab, Danish Dementia Research Centre, Department of Neurology, Rigshospitalet, University of Copenhagen, Denmark.
⁴ Stem Cells and Embryology Group, Department of Veterinary Clinical and Animal Sciences, Faculty of Health and Medical Sciences, University of Copenhagen, Denmark.
⁵ Stem Cells and Embryology Group, Department of Veterinary Clinical and Animal Sciences, Faculty of Health and Medical Sciences, University of Copenhagen, Denmark. Electronic address: kkf@sund.ku.dk.

PMID: 27558613
DOI: 10.1016/j.scr.2016.06.004

Abstract

Frontotemporal dementia (FTD) is an early onset neurodegenerative disease. Mutations in several genes cause familial FTD and one of them is charged multivesicular body protein 2B (CHMP2B) on chromosome 3 (FTD3), a component of the endosomal sorting complex required for transport III (ESCRT-III). We have generated an induced pluripotent stem cell (iPSC) line of a healthy individual and inserted the CHMP2B IVS5AS G-C gene mutation into one of the alleles, resulting in aberrant splicing. This human iPSC line provides an ideal model to study CHMP2B-dependent phenotypes of FTD3.