In vivo characterization of skeletal muscle function in nebulin‐deficient mice

Abstract

Introduction The conditional nebulin knockout mouse is a new model mimicking nemaline myopathy, a rare disease characterized by muscle weakness and rods within muscle fibers. We investigated the impact of nebulin (NEB) deficiency on muscle function in vivo. Methods Conditional nebulin knockout mice and control littermates were studied at 10 to 12 months. Muscle function (force and fatigue) and anatomy (muscles volume and fat content) were measured in vivo. Myosin heavy chain (MHC) composition and nebulin (NEB) protein expression were assessed by protein electrophoresis. Results Conditional nebulin knockout mice displayed a lower NEB level (−90%) leading to a 40% and 45% reduction in specific maximal force production and muscles volume, respectively. Nebulin deficiency was also associated with higher resistance to fatigue and increased MHC I content. Discussion Adult nebulin‐deficient mice displayed severe muscle atrophy and weakness in vivo related to a low NEB content but an improved fatigue resistance due to a slower contractile phenotype.

Impaired aerobic capacity and premature fatigue preceding muscle weakness in the skeletal muscle Tfam-knockout mouse model

“…This reduced cost would be due to a reduced sarcoplasmic reticulum (SR) calcium (Ca 2+ ) release resulting in a decreased activation of the energy-consuming cross-bridges and SR Ca 2+ pumps (Aydin Disease Models & Mechanisms • DMM • Accepted manuscript Wredenberg et al, 2002). A similar lack of effect on muscle fatigue has been previously demonstrated in nemaline myopathy mouse models that also display a severe muscle weakness (Gineste et al, 2013;Gineste et al, 2020) and might then be due to the fact that experiments have been conducted in relatively late stages of the disease, i.e., when severe muscle weakness was established and the resulting energy consumption during contractions was decreased. Accordingly, premature fatigue (i.e., faster drop in force) related to decreased mitochondrial oxidative capacity has been shown to precede overt muscle weakness in mouse models with mitochondrial dysfunction as well as in patients with mitochondrial myopathies (Finsterer, 2020;Tarnopolsky, 2016;Yamada et al, 2012).…”

Adaptation to full weight‐bearing following disuse in rats: The impact of biological sex on musculoskeletal recovery

“…Anesthetized animals connected to the footplate apparatus were subjected to a fatigue plantar flexion protocol, where they received a 120 s stimulation train (frequency: 40 Hz, pulse duration: 200 ms, pulse delay: 800 ms, repetitions: 120) as described elsewhere (Bagni et al., 2019 ; Fuglevand et al., 1999 ; Gineste et al., 2020 ). The maximal force produced during the protocol was recorded, and the AUC of the force curve was calculated.…”

Integrative Analysis of Nanopore and Illumina Sequencing Reveals Alternative Splicing Complexity in Pig Longissimus Dorsi Muscle

“…MYBPC2 is involved in the regulation of actin binding, protein binding, muscle structural components, cell adhesion, and myofilament sliding ( Chen et al, 2021 ). NEB is a structural component of sarcomeres that extend along filaments and regulate key functions of skeletal muscle ( Gineste et al, 2020 ). In pig longissimus dorsi samples, genes related to skeletal muscle function produced numerous splicing isoforms, and skeletal muscle fibers were also found to be a factor affecting IMF deposition ( Veloso et al, 2018 ), suggesting that AS plays an important role in muscle contraction and activity.…”