Deregulated Ca²⁺ cycling underlies the development of arrhythmia and heart disease due to mutant obscurin.

ABSTRACT: Obscurins are cytoskeletal proteins with structural and regulatory roles encoded by OBSCN. Mutations in OBSCN are associated with the development of hypertrophic cardiomyopathy (HCM) and dilated cardiomyopathy (DCM). Specifically, the R4344Q mutation present in immunoglobulin domain 58 (Ig58) was the first to be linked with the development of HCM. To assess the effects of R4344Q in vivo, we generated the respective knock-in mouse model. Mutant obscurins are expressed and incorporated normally into sarcomeres. The expression patterns of sarcomeric and Ca²⁺-cycling proteins are unaltered in sedentary 1-year-old knock-in myocardia, with the exception of sarco/endoplasmic reticulum Ca²⁺ adenosine triphosphatase 2 (SERCA2) and pentameric phospholamban whose l

SUBMITTER: Hu LR 

PROVIDER: S-EPMC5462502 | biostudies-literature | 2017 Jun

REPOSITORIES: biostudies-literature