Generation of two isogenic control lines by correcting the BAG3 P209L mutation of human induced pluripotent stem cell (hiPSC) lines from patients with myofibrillar myopathy-6

Kerstin Filippi; Martin Wiemann; Bernd K Fleischmann; Michael Hesse

doi:10.1016/j.scr.2024.103627

Generation of two isogenic control lines by correcting the BAG3 P209L mutation of human induced pluripotent stem cell (hiPSC) lines from patients with myofibrillar myopathy-6

Stem Cell Res. 2024 Dec 7:82:103627. doi: 10.1016/j.scr.2024.103627. Online ahead of print.

Authors

Kerstin Filippi¹, Martin Wiemann¹, Bernd K Fleischmann¹, Michael Hesse²

Affiliations

¹ Institute of Physiology I, Medical Faculty, University of Bonn, Germany.
² Institute of Physiology I, Medical Faculty, University of Bonn, Germany. Electronic address: [email protected].

PMID: 39662463
DOI: 10.1016/j.scr.2024.103627

Abstract

BAG3 plays a key role in proteostasis as a central component of the chaperone-assisted selective autophagy (CASA) complex. A point mutation (p.P209L; c.626C>T) in the BAG3 gene causes severe myofibrillar myopathy-6 (MFM6), restrictive cardiomyopathy and polyneuropathy leading to muscle weakness and heart failure. Establishing suitable controls for patient-derived BAG3^P209L/WT-induced pluripotent stem cells (iPSCs), two isogenic controls were generated by correcting the point mutation c.626C>T in iPSCs from two MFM6-patients. We performed quality control of these lines by differentiation into the three germ layers and pluripotency tests. These isogenic hiPSC-control lines allow the correct analysis of MFM6 using corresponding patient-specific iPSCs.