Because type I muscle fibers express the same myosin isoform as cardiac muscle (Myh7), the effect of omecamtiv mecarbil (OM), a small molecule activator of Myh7, was studied in a nebulin-based NEM mouse model (Neb cKO).
Recently, mutations in KBTBD13, KLHL40 and KLHL41, three substrate adaptors for the E3-ubiquitin ligase Cullin-3, have been associated with early-onset nemaline myopathies.
Recently, mutations in KBTBD13, KLHL40 and KLHL41, three substrate adaptors for the E3-ubiquitin ligase Cullin-3, have been associated with early-onset nemaline myopathies.
Recently, mutations in KBTBD13, KLHL40 and KLHL41, three substrate adaptors for the E3-ubiquitin ligase Cullin-3, have been associated with early-onset nemaline myopathies.
Taken together, our data highlight the importance for Cullin-3 mediated degradation of ACTN1 for muscle development, and indicate a new pathomechanism for the etiology of myopathies seen in Cullin-3 knockout mice and nemaline myopathy patients.
Here, we describe a role of NM causing Kelch protein, KLHL41, in premyofibil-myofibil transition during skeletal muscle development through a regulation of the thin filament chaperone, nebulin related anchoring protein (NRAP).
Characterization of these mice revealed that the truncation caused a moderate myopathy phenotype reminiscent of nemaline myopathy despite the majority of nebulin being localized properly in the thin filaments.
Our recent work has identified a variable degree of behavioral benefit when treating 2 NM mouse models due to mutations in Acta1 with myostatin inhibition.
This study is focused on the effects of delivering ActRIIB-mFc (Acceleron; a myostatin inhibitor) to the nebulin conditional knockout KO (Neb cKO) mouse model of NM.
L-tyrosine supplementation does not ameliorate skeletal muscle dysfunction in zebrafish and mouse models of dominant skeletal muscle α-actinnemaline myopathy.
The type 1 fiber atrophy and clusters of rods in normal size muscle fibers supported the diagnosis of congenital NM and prompted genetic molecular testing, which led to discovery of the novel ACTA1 variant causative of the myopathy.
Loss of skeletal α-actin results in nemaline myopathy and we have previously shown that the pathological symptoms of the disease and reduction in muscle performance are recapitulated in a zebrafish antisense morpholino knockdown model.