Derivation of MYBPC3-knockout iPSC that Display a Cardiomyopathy Phenotype
(A) Exon 24 of MYBPC3 was targeted by CRISPR/Cas9 and Sanger sequencing of one clone PGPC17_11-MYBPC3#4 (hereby identified as MYBPC3_KO) identified an out-of-frame insertion resulting in an early stop codon.
(B) Normal karyotype was confirmed before differentiation and characterization.
(C) Western blot probing for MYBPC3 using iPSC lysate as a negative control and parental CM lysate as a positive control. No full-length or truncated forms of MYBPC3 were detected on the blot using near infrared detection. Revert total protein stain was used to show similar amounts of protein were added to each lane.
(D) Representative xCELLigence traces of PGPC17 and MYBPC3-KO CMs showing beat amplitude (cell index) and extracellular voltage recordings over a 20-s sweep at D40 (independent experiments = 2; technical replicates ≥8). MYBPC3-KO CMs showed a higher beat amplitude compared with isogenic control CMs suggestive of hypercontractility as seen in hypertrophic cardiomyopathy.