Articles

Are mice good models for human neuromuscular disease? Comparing muscle excursions in walking between mice and humans

The mouse is one of the most widely used animal models to study neuromuscular diseases and test new therapeutic strategies. However, findings from successful pre-clinical studies using mouse models frequently ...

Authors: Xiao Hu, James P. Charles, Turgay Akay, John R. Hutchinson and Silvia S. Blemker

A mouse anti-myostatin antibody increases muscle mass and improves muscle strength and contractility in the mdx mouse model of Duchenne muscular dystrophy and its humanized equivalent, domagrozumab (PF-06252616), increases muscle volume in cynomolgus monkeys

The treatments currently approved for Duchenne muscular dystrophy (DMD), a progressive skeletal muscle wasting disease, address the needs of only a small proportion of patients resulting in an urgent need for ...

Authors: Michael St. Andre, Mark Johnson, Prashant N. Bansal, Jeremy Wellen, Andrew Robertson, Alan Opsahl, Peter M. Burch, Peter Bialek, Carl Morris and Jane Owens

The breaking and making of healthy adult human skeletal muscle in vivo

While muscle regeneration has been extensively studied in animal and cell culture models, in vivo myogenesis in adult human skeletal muscle has not been investigated in detail.

Authors: Abigail L. Mackey and Michael Kjaer

Treatment with the anti-IL-6 receptor antibody attenuates muscular dystrophy via promoting skeletal muscle regeneration in dystrophin-/utrophin-deficient mice

Chronic increases in the levels of the inflammatory cytokine interleukin-6 (IL-6) in serum and skeletal muscle are thought to contribute to the progression of muscular dystrophy. Dystrophin/utrophin double-kno...

Authors: Eiji Wada, Jun Tanihata, Akira Iwamura, Shin’ichi Takeda, Yukiko K. Hayashi and Ryoichi Matsuda

Utrophin influences mitochondrial pathology and oxidative stress in dystrophic muscle

Duchenne muscular dystrophy (DMD) is a lethal X-linked muscle wasting disorder caused by the absence of dystrophin, a large cytoskeletal muscle protein. Increasing the levels of the dystrophin-related-protein ...

Authors: Tahnee L. Kennedy, Lee Moir, Sarah Hemming, Ben Edwards, Sarah Squire, Kay Davies and Simon Guiraud

Loss of MKP-5 promotes myofiber survival by activating STAT3/Bcl-2 signaling during regenerative myogenesis

The mitogen-activated protein kinases (MAPKs) have been shown to be involved in regulating myofiber survival. In skeletal muscle, p38 MAPK and JNK are negatively regulated by MAPK phosphatase-5 (MKP-5). During...

Authors: Kisuk Min, Ahmed Lawan and Anton M. Bennett

HGF potentiates extracellular matrix-driven migration of human myoblasts: involvement of matrix metalloproteinases and MAPK/ERK pathway

The hepatocyte growth factor (HGF) is required for the activation of muscle progenitor cells called satellite cells (SC), plays a role in the migration of proliferating SC (myoblasts), and is present as a solu...

Authors: Mariela Natacha González, Wallace de Mello, Gillian S. Butler-Browne, Suse Dayse Silva-Barbosa, Vincent Mouly, Wilson Savino and Ingo Riederer

Increased plasma lipid levels exacerbate muscle pathology in the mdx mouse model of Duchenne muscular dystrophy

Duchenne muscular dystrophy (DMD) is caused by loss of dystrophin expression and leads to severe ambulatory and cardiac function decline. However, the dystrophin-deficient mdx murine model of DMD only develops a ...

Authors: Nadia Milad, Zoe White, Arash Y. Tehrani, Stephanie Sellers, Fabio M.V. Rossi and Pascal Bernatchez

Fragile X mental retardation protein regulates skeletal muscle stem cell activity by regulating the stability of Myf5 mRNA

Regeneration of adult tissues relies on adult stem cells that are primed to enter a differentiation program, while typically remaining quiescent. In mouse skeletal muscle, these features are reconciled by mult...

Authors: Ryo Fujita, Victoria Zismanov, Jean-Marie Jacob, Solène Jamet, Krum Asiev and Colin Crist

Mice overexpressing growth hormone exhibit increased skeletal muscle myostatin and MuRF1 with attenuation of muscle mass

In contrast to the acute effects of growth hormone (GH) on skeletal muscle protein synthesis, long-term GH treatment appears to have negligible effects on muscle mass. Despite this knowledge, little is known r...

Authors: Leslie A. Consitt, Alicson Saneda, Gunjan Saxena, Edward O. List and John J. Kopchick

BET bromodomain inhibitors and agonists of the beta-2 adrenergic receptor identified in screens for compounds that inhibit DUX4 expression in FSHD muscle cells

Facioscapulohumeral dystrophy (FSHD) is a progressive muscle disease caused by mutations that lead to epigenetic derepression and inappropriate transcription of the double homeobox 4 (DUX4) gene in skeletal muscl...

Authors: Amy E. Campbell, Jonathan Oliva, Matthew P. Yates, Jun Wen Zhong, Sean C. Shadle, Lauren Snider, Nikita Singh, Shannon Tai, Yosuke Hiramuki, Rabi Tawil, Silvère M. van der Maarel, Stephen J. Tapscott and Francis M. Sverdrup

Exome sequencing reveals independent SGCD deletions causing limb girdle muscular dystrophy in Boston terriers

Limb-girdle muscular dystrophies (LGMDs) are a heterogeneous group of inherited autosomal myopathies that preferentially affect voluntary muscles of the shoulders and hips. LGMD has been clinically described i...

Authors: Melissa L. Cox, Jacquelyn M. Evans, Alexander G. Davis, Ling T. Guo, Jennifer R. Levy, Alison N. Starr-Moss, Elina Salmela, Marjo K. Hytönen, Hannes Lohi, Kevin P. Campbell, Leigh Anne Clark and G. Diane Shelton

Differential requirement for satellite cells during overload-induced muscle hypertrophy in growing versus mature mice

Pax7+ satellite cells are required for skeletal muscle fiber growth during post-natal development in mice. Satellite cell-mediated myonuclear accretion also appears to persist into early adulthood. Given the i...

Authors: Kevin A. Murach, Sarah H. White, Yuan Wen, Angel Ho, Esther E. Dupont-Versteegden, John J. McCarthy and Charlotte A. Peterson

Expression patterns of FSHD-causing DUX4 and myogenic transcription factors PAX3 and PAX7 are spatially distinct in differentiating human stem cell cultures

Facioscapulohumeral muscular dystrophy (FSHD) is most commonly inherited in an autosomal dominant pattern and caused by the abnormal expression of DUX4 in skeletal muscle. The DUX4 transcription factor has DNA...

Authors: Premi Haynes, Kelly Kernan, Suk-Lin Zhou and Daniel G. Miller

SMCHD1 regulates a limited set of gene clusters on autosomal chromosomes

Facioscapulohumeral muscular dystrophy (FSHD) is in most cases caused by a contraction of the D4Z4 macrosatellite repeat on chromosome 4 (FSHD1) or by mutations in the SMCHD1 or DNMT3B gene (FSHD2). Both situatio...

Authors: Amanda G. Mason, Roderick C. Slieker, Judit Balog, Richard J. L. F. Lemmers, Chao-Jen Wong, Zizhen Yao, Jong-Won Lim, Galina N. Filippova, Enrico Ne, Rabi Tawil, Bas T. Heijmans, Stephen J. Tapscott and Silvère M. van der Maarel

Nanospan, an alternatively spliced isoform of sarcospan, localizes to the sarcoplasmic reticulum in skeletal muscle and is absent in limb girdle muscular dystrophy 2F

Sarcospan (SSPN) is a transmembrane protein that interacts with the sarcoglycans (SGs) to form a tight subcomplex within the dystrophin-glycoprotein complex that spans the sarcolemma and interacts with laminin...

Authors: Angela K. Peter, Gaynor Miller, Joana Capote, Marino DiFranco, Alhondra Solares-Pérez, Emily L. Wang, Jim Heighway, Ramón M. Coral-Vázquez, Julio Vergara and Rachelle H. Crosbie-Watson

Complement C5a-C5aR1 signalling drives skeletal muscle macrophage recruitment in the hSOD1^G93A mouse model of amyotrophic lateral sclerosis

The terminal pathway of the innate immune complement system is implicated in the pathogenesis of amyotrophic lateral sclerosis (ALS). Terminal complement activation leads to generation of C5a, which through it...

Authors: Haitao A. Wang, John D. Lee, Kah Meng Lee, Trent M. Woodruff and Peter G. Noakes

The golden retriever model of Duchenne muscular dystrophy

Duchenne muscular dystrophy (DMD) is an X-linked disease caused by mutations in the DMD gene and loss of the protein dystrophin. The absence of dystrophin leads to myofiber membrane fragility and necrosis, with e...

Authors: Joe N. Kornegay

Unexpected evolutionarily conserved rapid effects of viral infection on oxytocin receptor and TGF-β/pSmad3

shRNA lentiviral vectors are extensively used for gene knockdowns in mammalian cells, and non-target shRNAs typically are considered the proper experimental control for general changes caused by RNAi. However,...

Authors: Yutong Liu and Irina Conboy

Retinoid acid-induced microRNA-31-5p suppresses myogenic proliferation and differentiation by targeting CamkIIδ

We previously reported that Wnt5a/CaMKIIδ (calcium/calmodulin-dependent protein kinase II delta) pathway was involved in the embryonic tongue deformity induced by excess retinoic acid (RA). Our latest study fo...

Authors: Bo Liu, Chao Liu, Wei Cong, Nan Li, Nan Zhou, Yi Tang, Chao Wei, Han Bai, Ying Zhang and Jing Xiao

Absence of physiological Ca²⁺ transients is an initial trigger for mitochondrial dysfunction in skeletal muscle following denervation

Motor neurons control muscle contraction by initiating action potentials in muscle. Denervation of muscle from motor neurons leads to muscle atrophy, which is linked to mitochondrial dysfunction. It is known t...

Authors: Chehade Karam, Jianxun Yi, Yajuan Xiao, Kamal Dhakal, Lin Zhang, Xuejun Li, Carlo Manno, Jiejia Xu, Kaitao Li, Heping Cheng, Jianjie Ma and Jingsong Zhou

Linkages between changes in the 3D organization of the genome and transcription during myotube differentiation in vitro

The spatial organization of eukaryotic genomes facilitates and reflects the underlying nuclear processes that are occurring in the cell. As such, the spatial organization of a genome represents a window on the...

Authors: Malina D. Doynova, James F. Markworth, David Cameron-Smith, Mark H. Vickers and Justin M. O’Sullivan

Erratum to: Voluntary resistance wheel exercise from mid-life prevents sarcopenia and increases markers of mitochondrial function and autophagy in muscles of old male and female C57BL/6J mice

Authors: Zoe White, Jessica Terrill, Robert B. White, Christopher McMahon, Phillip Sheard, Miranda D. Grounds and Tea Shavlakadze

Deletion of the Ste20-like kinase SLK in skeletal muscle results in a progressive myopathy and muscle weakness

The Ste20-like kinase, SLK, plays an important role in cell proliferation and cytoskeletal remodeling. In fibroblasts, SLK has been shown to respond to FAK/Src signaling and regulate focal adhesion turnover th...

Authors: Benjamin R. Pryce, Khalid N. Al-Zahrani, Sébastien Dufresne, Natalya Belkina, Cédrik Labrèche, Genaro Patino-Lopez, Jérôme Frenette, Stephen Shaw and Luc A. Sabourin

Inhibition of Stat3 signaling ameliorates atrophy of the soleus muscles in mice lacking the vitamin D receptor

Although skeletal muscle wasting has long been observed as a clinical outcome of impaired vitamin D signaling, precise molecular mechanisms that mediate the loss of muscle mass in the absence of vitamin D sign...

Authors: Suchitra D. Gopinath

A novel method for the quantification of fatty infiltration in skeletal muscle

Fatty infiltration of the skeletal muscle is a common but poorly understood feature of many myopathies. It is best described in human muscle, where non-invasive imaging techniques and representative histology ...

Authors: Nicole K. Biltz and Gretchen A. Meyer

Voluntary resistance wheel exercise from mid-life prevents sarcopenia and increases markers of mitochondrial function and autophagy in muscles of old male and female C57BL/6J mice

There is much interest in the capacity of resistance exercise to prevent the age-related loss of skeletal muscle mass and function, known as sarcopenia. This study investigates the molecular basis underlying t...

Authors: Zoe White, Jessica Terrill, Robert B. White, Christopher McMahon, Phillip Sheard, Miranda D. Grounds and Tea Shavlakadze

Laminin 521 maintains differentiation potential of mouse and human satellite cell-derived myoblasts during long-term culture expansion

Large-scale expansion of myogenic progenitors is necessary to support the development of high-throughput cellular assays in vitro and to advance genetic engineering approaches necessary to develop cellular the...

Authors: Christopher M. Penton, Vasudeo Badarinarayana, Joy Prisco, Elaine Powers, Mark Pincus, Ronald E. Allen and Paul R. August

Skeletal muscle characteristics are preserved in hTERT/cdk4 human myogenic cell lines

hTERT/cdk4 immortalized myogenic human cell lines represent an important tool for skeletal muscle research, being used as therapeutically pertinent models of various neuromuscular disorders and in numerous fun...

Authors: Matthew Thorley, Stéphanie Duguez, Emilia Maria Cristina Mazza, Sara Valsoni, Anne Bigot, Kamel Mamchaoui, Brennan Harmon, Thomas Voit, Vincent Mouly and William Duddy

CCAAT/enhancer binding protein β is required for satellite cell self-renewal

Postnatal growth and repair of skeletal muscle relies upon a population of quiescent muscle precursor cells, called satellite cells that can be activated to proliferate and differentiate into new myofibers, as...

Authors: Neena Lala-Tabbert, Hamood AlSudais, François Marchildon, Dechen Fu and Nadine Wiper-Bergeron

Muscle PGC-1α modulates satellite cell number and proliferation by remodeling the stem cell niche

The myogenic capacity of satellite cells (SCs), adult muscle stem cells, is influenced by aging, exercise, and other factors. In skeletal muscle, the peroxisome proliferator-activated receptor γ coactivator 1α...

Authors: Ivana Dinulovic, Regula Furrer, Markus Beer, Arnaud Ferry, Bettina Cardel and Christoph Handschin

Nuclear bodies reorganize during myogenesis in vitro and are differentially disrupted by expression of FSHD-associated DUX4

Nuclear bodies, such as nucleoli, PML bodies, and SC35 speckles, are dynamic sub-nuclear structures that regulate multiple genetic and epigenetic processes. Additional regulation is provided by RNA/DNA handlin...

Authors: Sachiko Homma, Mary Lou Beermann, Bryant Yu, Frederick M. Boyce and Jeffrey Boone Miller

Heme oxygenase and carbon monoxide protect from muscle dystrophy

Duchenne muscle dystrophy (DMD) is one of the most common lethal genetic diseases of children worldwide and is 100% fatal. Steroids, the only therapy currently available, are marred by poor efficacy and a high...

Authors: Mun Chun Chan, Olivia Ziegler, Laura Liu, Glenn C. Rowe, Saumya Das, Leo E. Otterbein and Zoltan Arany

PGC-1α modulates necrosis, inflammatory response, and fibrotic tissue formation in injured skeletal muscle

Skeletal muscle tissue has an enormous regenerative capacity that is instrumental for a successful defense against muscle injury and wasting. The peroxisome proliferator-activated receptor γ coactivator 1α (PG...

Authors: Ivana Dinulovic, Regula Furrer, Sabrina Di Fulvio, Arnaud Ferry, Markus Beer and Christoph Handschin

Established cell surface markers efficiently isolate highly overlapping populations of skeletal muscle satellite cells by fluorescence-activated cell sorting

Fluorescent-activated cell sorting (FACS) has enabled the direct isolation of highly enriched skeletal muscle stem cell, or satellite cell, populations from postnatal tissue. Several distinct surface marker pa...

Authors: Claire C. Maesner, Albert E. Almada and Amy J. Wagers

Erratum to: Increased microenvironment stiffness in damaged myofibers promotes myogenic progenitor cell proliferation

Authors: Frédéric Trensz, Fabrice Lucien, Vanessa Couture, Thomas Söllradl, Geneviève Drouin, André-Jean Rouleau, Michel Grandbois, Gregory Lacraz and Guillaume Grenier

Muscle-specific deletion of SOCS3 increases the early inflammatory response but does not affect regeneration after myotoxic injury

Muscles of old animals are injured more easily and regenerate poorly, attributed in part to increased levels of circulating pro-inflammatory cytokines. The Janus kinase/signal transducers and activators of tra...

Authors: Kristy Swiderski, Savant S. Thakur, Timur Naim, Jennifer Trieu, Annabel Chee, David I. Stapleton, René Koopman and Gordon S. Lynch

The functional significance of the skeletal muscle clock: lessons from Bmal1 knockout models

The circadian oscillations of muscle genes are controlled either directly by the intrinsic muscle clock or by extrinsic factors, such as feeding, hormonal signals, or neural influences, which are in turn regul...

Authors: Stefano Schiaffino, Bert Blaauw and Kenneth A. Dyar

VAChT overexpression increases acetylcholine at the synaptic cleft and accelerates aging of neuromuscular junctions

Cholinergic dysfunction occurs during aging and in a variety of diseases, including amyotrophic lateral sclerosis (ALS). However, it remains unknown whether changes in cholinergic transmission contributes to a...

Authors: Satoshi Sugita, Leland L. Fleming, Caleb Wood, Sydney K. Vaughan, Matheus P. S. M. Gomes, Wallace Camargo, Ligia A. Naves, Vania F. Prado, Marco A. M. Prado, Cristina Guatimosim and Gregorio Valdez

Loss of niche-satellite cell interactions in syndecan-3 null mice alters muscle progenitor cell homeostasis improving muscle regeneration

The skeletal muscle stem cell niche provides an environment that maintains quiescent satellite cells, required for skeletal muscle homeostasis and regeneration. Syndecan-3, a transmembrane proteoglycan express...

Authors: Addolorata Pisconti, Glen B. Banks, Farshad Babaeijandaghi, Nicole Dalla Betta, Fabio M. V. Rossi, Jeffrey S. Chamberlain and Bradley B. Olwin

Direct reprogramming of urine-derived cells with inducible MyoD for modeling human muscle disease

Cellular models of muscle disease are taking on increasing importance with the large number of genes and mutations implicated in causing myopathies and the concomitant need to test personalized therapies. Deve...

Authors: Ellis Y. Kim, Patrick Page, Lisa M. Dellefave-Castillo, Elizabeth M. McNally and Eugene J. Wyatt

Six1 homeoprotein drives myofiber type IIA specialization in soleus muscle

Adult skeletal muscles are composed of slow and fast myofiber subtypes which each express selective genes required for their specific contractile and metabolic activity. Six homeoproteins are transcription fac...

Authors: Iori Sakakibara, Maud Wurmser, Matthieu Dos Santos, Marc Santolini, Serge Ducommun, Romain Davaze, Anthony Guernec, Kei Sakamoto and Pascal Maire

Failed reinnervation in aging skeletal muscle

Skeletal muscle displays a marked accumulation of denervated myofibers at advanced age, which coincides with an acceleration of muscle atrophy.

Authors: Sudhakar Aare, Sally Spendiff, Madhusudanarao Vuda, Daren Elkrief, Anna Perez, Qinghua Wu, Dominique Mayaki, Sabah N. A. Hussain, Stefan Hettwer and Russell T. Hepple

p38α MAPK disables KMT1A-mediated repression of myogenic differentiation program

Master transcription factor MyoD can initiate the entire myogenic gene expression program which differentiates proliferating myoblasts into multinucleated myotubes. We previously demonstrated that histone meth...

Authors: Biswanath Chatterjee, David W. Wolff, Mathivanan Jothi, Munmun Mal and Asoke K. Mal

Embracing change: striated-for-smooth muscle replacement in esophagus development

The esophagus functions to transport food from the oropharyngeal region to the stomach via waves of peristalsis and transient relaxation of the lower esophageal sphincter. The gastrointestinal tract, including...

Authors: Robert S. Krauss, Daisuke Chihara and Anthony I. Romer

ActRII blockade protects mice from cancer cachexia and prolongs survival in the presence of anti-cancer treatments

Cachexia affects the majority of patients with advanced cancer and is associated with reduced treatment tolerance, response to therapy, quality of life, and life expectancy. Cachectic patients with advanced ca...

Authors: Shinji Hatakeyama, Serge Summermatter, Marie Jourdain, Stefan Melly, Giulia C. Minetti and Estelle Lach-Trifilieff

Dystrophin restoration therapy improves both the reduced excitability and the force drop induced by lengthening contractions in dystrophic mdx skeletal muscle

The greater susceptibility to contraction-induced skeletal muscle injury (fragility) is an important dystrophic feature and tool for testing preclinic dystrophin-based therapies for Duchenne muscular dystrophy...

Authors: Pauline Roy, Fredérique Rau, Julien Ochala, Julien Messéant, Bodvael Fraysse, Jeanne Lainé, Onnik Agbulut, Gillian Butler-Browne, Denis Furling and Arnaud Ferry

Characterization of a Dmd ^EGFP reporter mouse as a tool to investigate dystrophin expression

Dystrophin is a rod-shaped cytoplasmic protein that provides sarcolemmal stability as a structural link between the cytoskeleton and the extracellular matrix via the dystrophin-associated protein complex (DAPC...

Authors: Mina V. Petkova, Susanne Morales-Gonzales, Karima Relizani, Esther Gill, Franziska Seifert, Josefine Radke, Werner Stenzel, Luis Garcia, Helge Amthor and Markus Schuelke

Progressive impairment of Ca_V1.1 function in the skeletal muscle of mice expressing a mutant type 1 Cu/Zn superoxide dismutase (G93A) linked to amyotrophic lateral sclerosis

Amyotrophic lateral sclerosis (ALS) is an adult-onset neurodegenerative disorder that is typically fatal within 3–5 years of diagnosis. While motoneuron death is the defining characteristic of ALS, the events ...

Authors: Donald Beqollari, Christin F. Romberg, Gabriella Dobrowolny, Martina Martini, Andrew A. Voss, Antonio Musarò and Roger A. Bannister

Treatment with rGDF11 does not improve the dystrophic muscle pathology of mdx mice

Duchenne muscular dystrophy (DMD) is an inherited lethal muscle wasting disease characterized by cycles of degeneration and regeneration, with no effective therapy. Growth differentiation factor 11 (GDF11), a ...

Authors: Fabrizio Rinaldi, Yu Zhang, Ricardo Mondragon-Gonzalez, Jeffrey Harvey and Rita C. R. Perlingeiro