biostudies-literatureRaad NNIA NIH HHSNHLBI NIH HHS441-454https://www.ebi.ac.uk/biostudies/studies/S-EPMC8456417biostudies-literatureUnknown144(6)<h4>Background</h4>Arginine (Arg) 14 deletion (R14del) in the calcium regulatory protein phospholamban (hPLN^R14del) has been identified as a disease-causing mutation in patients with an inherited cardiomyopathy. Mechanisms underlying the early arrhythmogenic phenotype that predisposes carriers of this mutation to sudden death with no apparent structural remodeling remain unclear.<h4>Methods</h4>To address this, we performed high spatiotemporal resolution optical mapping of intact hearts from adult knock-in mice harboring the human PLN^WT (wildtype [WT], n=12) or the heterozygous human PLN^R14del mutation (R14del, n=12) before and after ex vivo challenge with isoproterenol and rapid pacing.<h4>Results</h4>Adverse electrophysiological remodeling was evident in CirculationArrhythmia Mechanism and Dynamics in a Humanized Mouse Model of Inherited Cardiomyopathy Caused by Phospholamban R14del Mutation.PMC8456417R01 HL148008R01 HL137036R01 HL149344R21 AG054211R01 HL137259R01 HL131735Bittihn PCai CLJeong DCeholski DZhang LIlkan ZKranias EGCacheux MAkar FGRaad NKohlbrenner EStillitano FHajjar RJfalseArrhythmia Mechanism and Dynamics in a Humanized Mouse Model of Inherited Cardiomyopathy Caused by Phospholamban R14del Mutation.<h4>Background</h4>Arginine (Arg) 14 deletion (R14del) in the calcium regulatory protein phospholamban (hPLN^R14del) has been identified as a disease-causing mutation in patients with an inherited cardiomyopathy. Mechanisms underlying the early arrhythmogenic phenotype that predisposes carriers of this mutation to sudden death with no apparent structural remodeling remain unclear.<h4>Methods</h4>To address this, we performed high spatiotemporal resolution optical mapping of intact hearts from adult knock-in mice harboring the human PLN^WT (wildtype [WT], n=12) or the heterozygous human PLN^R14del mutation (R14del, n=12) before and after ex vivo challenge with isoproterenol and rapid pacing.<h4>Results</h4>Adverse electrophysiological remodeling was evident in 2021-01-01T00:00:00Z2021 Aug2025-04-26T16:27:57.092Z2025-02-19T02:26:44.546ZS-EPMC84564173402411610.1161/circulationaha.119.04350210.1161/CIRCULATIONAHA.119.043502