Lamin A/C dysregulation contributes to cardiac pathology in a mouse model of severe spinal muscular atrophy.

ABSTRACT: Cardiac pathology is emerging as a prominent systemic feature of spinal muscular atrophy (SMA), but little is known about the underlying molecular pathways. Using quantitative proteomics analysis, we demonstrate widespread molecular defects in heart tissue from the Taiwanese mouse model of severe SMA. We identify increased levels of lamin A/C as a robust molecular phenotype in the heart of SMA mice and show that lamin A/C dysregulation is also apparent in SMA patient fibroblast cells and other tissues from SMA mice. Lamin A/C expression was regulated in vitro by knockdown of the E1 ubiquitination factor ubiquitin-like modifier activating enzyme 1, a key downstream mediator of SMN-dependent disease pathways, converging on β-catenin signaling. Increased levels of lamin A are known to increas

SUBMITTER: Soltic D 

PROVIDER: S-EPMC6927462 | biostudies-literature | 2019 Nov

REPOSITORIES: biostudies-literature