Impairments in contractility and cytoskeletal organisation cause nuclear defects in nemaline myopathy.

ABSTRACT: Nemaline myopathy (NM) is a skeletal muscle disorder caused by mutations in genes that are generally involved in muscle contraction, in particular those related to the structure and/or regulation of the thin filament. Many pathogenic aspects of this disease remain largely unclear. Here, we report novel pathological defects in skeletal muscle fibres of mouse models and patients with NM: irregular spacing and morphology of nuclei; disrupted nuclear envelope; altered chromatin arrangement; and disorganisation of the cortical cytoskeleton. Impairments in contractility are the primary cause of these nuclear defects. We also establish the role of microtubule organisation in determining nuclear morphology, a phenomenon which is likely to contribute to nuclear alterations in this disease. Our resu

SUBMITTER: Ross JA 

PROVIDER: S-EPMC6689292 | biostudies-literature | 2019 Sep

REPOSITORIES: biostudies-literature