Myogenic program dysregulation is contributory to disease pathogenesis in spinal muscular atrophy.

Mutations in the survival motor neuron (SMN1) gene lead to the neuromuscular disease spinal muscular atrophy (SMA). Although SMA is primarily considered as a motor neuron disease, the importance of muscle defects in its pathogenesis has not been fully examined. We use both primary cell culture and two different SMA model mice to demonstrate that reduced levels of Smn lead to a profound disruption in the expression of myogenic genes.

Mechanical efficiency of treadmill running exercise: effect of anaerobic-energy contribution at various speeds.

Objectives: Mechanical efficiency (ME) describes the ratio between mechanical (PMECH) and metabolic (PMET) power. The purpose of the study was to include an estimation of anaerobic energy expenditure (AnE) into the quantification of PMET using the accumulated oxygen deficit (AOD) and to examine its effect on the value of ME in treadmill running at submaximal, maximal, and supramaximal running speeds.

Methods: Participants (N = 11) underwent a graded maximal exercise test to determine velocity at peak oxygen uptake (vVO2peak).

Hearts of dystonia musculorum mice display normal morphological and histological features but show signs of cardiac stress.

Dystonin is a giant cytoskeletal protein belonging to the plakin protein family and is believed to crosslink the major filament systems in contractile cells. Previous work has demonstrated skeletal muscle defects in dystonin-deficient dystonia musculorum (dt) mice. In this study, we show that the dystonin muscle isoform is localized at the Z-disc, the H zone, the sarcolemma and intercalated discs in cardiac tissue.

Plakins in striated muscle.

Striated muscle cells contain numerous architectural proteins that contribute to the function of muscle as generators of mechanical force. Among these proteins are crosslinkers belonging to the plakin family, namely plectin, microtubule-actin crosslinking factor (ACF7/MACF1), bullous pemphigoid antigen 1 (Bpag1/dystonin), and desmoplakin. These plakin family members, in particular plectin and Bpag1/dystonin, exist as several isoforms.

Genetic alterations at the Bpag1 locus in dt mice and their impact on transcript expression.

The dystonin/Bpag1 gene encodes several tissue-specific alternatively spliced transcripts that encode cytoskeletal binding proteins. These various isoforms are necessary for maintaining the structural integrity of epithelial, neural, and muscle tissues. Mutations in the dystonin/Bpag1 gene cause dystonia musculorum (dt), a hereditary neuropathy of the mouse characterized by the progressive degeneration of sensory neurons.

Differentiation potential of primary myogenic cells derived from skeletal muscle of dystonia musculorum mice.

The dystonia musculorum (dt) mouse has a mutation in the gene encoding the cytoskeletal crosslinker protein bullous pemphigoid antigen 1 (Bpag1). These mice have perturbations in the cytoarchitecture of skeletal muscle. Bpag1 has been hypothesized to be involved in the maintenance rather than the establishment of the muscle cell architecture given that cytoskeletal disruptions are observed in the muscle tissue of post-natal dt mice.