Generation and characterization of an isogenic control line by correcting the BAG3 P209L mutation of a human induced pluripotent stem cell (hiPSC) line from a patient with myofibrillar myopathy-6

Kerstin Filippi; Isabelle Riße; Luke M Judge; Bruce R Conklin; Bernd K Fleischmann; Michael Hesse

doi:10.1016/j.scr.2024.103626

Generation and characterization of an isogenic control line by correcting the BAG3 P209L mutation of a human induced pluripotent stem cell (hiPSC) line from a patient with myofibrillar myopathy-6

Stem Cell Res. 2024 Dec 9:82:103626. doi: 10.1016/j.scr.2024.103626. Online ahead of print.

Authors

Kerstin Filippi¹, Isabelle Riße¹, Luke M Judge², Bruce R Conklin², Bernd K Fleischmann¹, Michael Hesse³

Affiliations

¹ Institute of Physiology I, Medical Faculty, University of Bonn, Germany.
² Gladstone Institutes, San Francisco, USA; University of California, San Francisco, USA.
³ Institute of Physiology I, Medical Faculty, University of Bonn, Germany. Electronic address: [email protected].

PMID: 39662461
DOI: 10.1016/j.scr.2024.103626

Abstract

BAG3 is a central component of the chaperone-assisted selective autophagy complex and thus important for proteostasis. This function is affected by a point mutation (p.P209L; c.626C>T) in the BAG3 gene, leading to myofibrillar myopathy-6 (MFM6), restrictive cardiomyopathy and polyneuropathy, which manifests as severe skeletal muscle weakness and heart failure. The isogenic induced pluripotent stem cell (iPSC) control line was generated by correcting for c.626C>T in iPSCs from MFM6-patient. Quality control was achieved by testing for pluripotency and differentiation into the three germ layers. In conjunction with patient-specific MFM6 hiPSC, the isogenic hiPSC control line enable the correct analysis of MFM6.