A5059796141- Muscle Physiology and Disorders
- Adipose Tissue and Metabolism
- Exercise and Physiological Responses
- Muscle metabolism and nutrition
- Genetic Neurodegenerative Diseases
- Cardiomyopathy and Myosin Studies
- Muscle activation and electromyography studies
- Nuclear Structure and Function
- Neurogenetic and Muscular Disorders Research
- Cellular transport and secretion
- RNA Research and Splicing
- Sports Performance and Training
- Mitochondrial Function and Pathology
- Cardiovascular and exercise physiology
- Pain Mechanisms and Treatments
- Hormonal and reproductive studies
- Metabolism, Diabetes, and Cancer
- Ion channel regulation and function
- Tissue Engineering and Regenerative Medicine
- Immune Cell Function and Interaction
- Cardiovascular Effects of Exercise
- Diet and metabolism studies
- Genetics and Physical Performance
- Nerve injury and regeneration
- Advanced Sensor and Energy Harvesting Materials
Inserm
2015-2024
Université Paris Cité
2015-2024
Sorbonne Université
2015-2024
Institut de Myologie
2015-2024
Centre de Recherche en Myologie
2015-2024
Centre de Recherche Saint-Antoine
2024
Sorbonne Paris Cité
2012-2022
Centre National de la Recherche Scientifique
2010-2020
Délégation Paris 5
2011-2020
Institut National du Sport, de l'Expertise et de la Performance
2019-2020
Mammalian target of rapamycin (mTOR) is a key regulator cell growth that associates with raptor and rictor to form the mTOR complex 1 (mTORC1) mTORC2, respectively. Raptor required for oxidative muscle integrity, whereas dispensable. In this study, we show muscle-specific inactivation leads severe myopathy, resulting in premature death. mTOR-deficient muscles display metabolic changes similar those observed lacking raptor, including impaired metabolism, altered mitochondrial regulation,...
AMP-activated protein kinase (AMPK) is a sensor of cellular energy status that plays central role in skeletal muscle metabolism. We used muscle-specific AMPKα1α2 double-knockout (mdKO) mice to provide direct genetic evidence the physiological importance AMPK regulating exercise capacity, mitochondrial function, and contraction-stimulated glucose uptake. Exercise performance was significantly reduced mdKO mice, with reduction maximal force production fatigue resistance. An increase proportion...
Centronuclear myopathies (CNM) are congenital disorders associated with muscle weakness and abnormally located nuclei in skeletal muscle. An autosomal dominant form of CNM results from mutations the gene encoding dynamin 2 (DNM2), loss-of-function myotubularin (MTM1) result X-linked (XLCNM, also called myotubular myopathy), which promotes severe neonatal hypotonia early death. Currently, no effective treatments exist for XLCNM. Here, we found increased DNM2 levels XLCNM patients a mouse...
Antisense oligonucleotides (ASOs) targeting pathologic RNAs have shown promising therapeutic corrections for many genetic diseases including myotonic dystrophy (DM1). Thus, ASO strategies DM1 can abolish the toxic RNA gain-of-function mechanism caused by nucleus-retained mutant DMPK (DM1 protein kinase) transcripts containing CUG expansions (CUGexps). However, systemic use of ASOs this muscular disease remains challenging due to poor drug distribution skeletal muscle. To overcome limitation,...
Abstract Autosomal dominant centronuclear myopathy (AD-CNM) is due to mutations in the gene encoding dynamin 2 (DNM2) involved endocytosis and intracellular membrane trafficking. To understand pathomechanisms resulting from a DNM2 mutation, we generated knock-in mouse model expressing most frequent AD-CNM mutation (KI-Dnm2R465W). Heterozygous (HTZ) mice developed showing specific spatial temporal muscle involvement. In primarily prominently affected tibialis anterior muscle, impairment of...
Myotonic dystrophy type 1 (DM1) is caused by an unstable CTG repeat expansion in the 3′UTR of DM protein kinase (DMPK) gene. DMPK transcripts carrying CUG expansions form nuclear foci and affect splicing regulation various RNA transcripts. Furthermore, bidirectional transcription over gene non-conventional translation repeated have been described DM1. It clear now that this disease may involve multiple pathogenic pathways including changes expression, stability regulation, translation,...
The anabolic effects of androgens on skeletal muscles are thought to be mediated predominantly through the androgen receptor (AR), a member ligand-dependent nuclear superfamily. However, despite numerous studies performed in men and rodents, these remain poorly understood. To characterize signaling muscles, we generated mice which AR is selectively ablated myofibers. We show that myocytic controls androgen-induced insulin-like growth factor IEa (IGF-IEa) expression highly androgen-sensitive...
Selenoprotein N (SelN) deficiency causes a group of inherited neuromuscular disorders termed SEPN1-related myopathies (SEPN1-RM). Although the function SelN remains unknown, recent data demonstrated that it is dispensable for mouse embryogenesis and suggested its involvement in regulation ryanodine receptors and/or cellular redox homeostasis. Here, we investigate role satellite cell (SC) muscle regeneration, using Sepn1−/− model. Following cardiotoxin-induced injury, expression was strongly...
REDD1 (regulated in development and DNA damage response 1) has been proposed to inhibit the mechanistic target of rapamycin complex 1 (mTORC1) during vitro hypoxia. expression is low under basal conditions but highly increased several catabolic stresses, like hypoxia glucocorticoids. However, function seems be tissue stress dependent, its role skeletal muscle vivo poorly characterized. Here, we investigated effect deletion on mass, protein synthesis, proteolysis, mTORC1 signaling pathway...
Oculopharyngeal muscular dystrophy (OPMD) is an adult-onset disorder characterized by ptosis, dysphagia and proximal limb weakness. Autosomal-dominant OPMD caused a short (GCG)8–13 expansions within the first exon of poly(A)-binding protein nuclear 1 gene (PABPN1), leading to expanded polyalanine tract in mutated protein. Expanded PABPN1 forms insoluble aggregates nuclei skeletal muscle fibres. In order gain insight into different physiological processes affected muscles, we have used...
Abstract Myotonic Dystrophy type 1 (DM1) is a dominant neuromuscular disease caused by nuclear-retained RNAs containing expanded CUG repeats. These toxic alter the activities of RNA splicing factors resulting in alternative misregulation and muscular dysfunction. Here we show that abnormal DMD exon 78 found dystrophic muscles DM1 patients due to functional loss MBNL1 leads re-expression an embryonic dystrophin place adult isoform. Forced expression zebrafish using exon-skipping approach...
Abstract Oculopharyngeal muscular dystrophy (OPMD) is an autosomal dominant, late-onset muscle disorder characterized by ptosis, swallowing difficulties, proximal limb weakness and nuclear aggregates in skeletal muscles. OPMD caused a trinucleotide repeat expansion the PABPN1 gene that results N-terminal expanded polyalanine tract polyA-binding protein 1 (PABPN1). Here we show treatment of mouse model with adeno-associated virus-based therapy combining complete knockdown endogenous its...
Myostatin (Mstn) participates in the regulation of skeletal muscle size and has emerged as a regulator metabolism. Here, we hypothesized that lack myostatin profoundly depresses oxidative phosphorylation-dependent function. Toward this end, explored Mstn(-/-) mice model for constitutive absence AAV-mediated overexpression propeptide blockade adult wild-type mice. We show muscles from mice, although larger stronger, fatigue extremely rapidly. deficiency shifts aerobic toward anaerobic energy...
One of the most promising therapeutic approaches for familial amyotrophic lateral sclerosis linked to superoxide dismutase 1 (SOD1) is suppression toxic mutant SOD1 in affected tissues. Here, we report an innovative molecular strategy inducing substantial, widespread, and sustained reduction human (hSOD1) levels throughout body SOD1G93A mice, leading effects animals. Adeno-associated virus serotype rh10 vectors (AAV10) were used mediate exon skipping hSOD1 pre-mRNA by expression...
The ubiquitous clathrin heavy chain (CHC), the main component of clathrin-coated vesicles, is well characterized for its role in intracellular membrane traffic and endocytosis from plasma (PM). Here, we demonstrate that skeletal muscle CHC regulates formation maintenance PM–sarcomere attachment sites also known as costameres. We show forms large coated lattices associated with actin filaments muscle-specific isoform α-actinin at PM differentiated myotubes. Depletion myotubes induced a loss...
Myostatin regulates skeletal muscle size via the activin receptor IIB (ActRIIB). However, its effect on energy metabolism and energy-dependent function remains largely unexplored. This question needs to be solved urgently since various therapies for neuromuscular diseases based blockade of ActRIIB signaling are being developed. Here, we show in mice, that 4-month pharmacological abrogation by treatment with soluble ActRIIB-Fc triggers extreme fatigability. is associated elevated serum...
The transcriptional coregulators PGC-1α and PGC-1β modulate the expression of numerous partially overlapping genes involved in mitochondrial biogenesis energetic metabolism. physiological role is poorly understood skeletal muscle, a tissue high content to produce ATP levels required for sustained contractions. Here we determine muscle using mice, which selectively ablated myofibres at adulthood (PGC-1β((i)skm-/-) mice). We show that myofibre myosin heavy chain composition number, strength...
Thymic involution occurs in young adult male Wistar rats that have performed two runs to exhaustion (RTE) on a treadmill, separated by 24-h rest period, but not after single RTE. We were interested determining whether programmed cell death (or apoptosis) is responsible for the corresponding decrease T-cell numbers thymus. DNA fragmentation, which an early feature of apoptosis and easily detected agarose gel electrophoresis, was found rat thymocytes second RTE (the duration 1 approximately 5...
Duchenne muscular dystrophy is characterized by atrophy, fibrosis, and fat accumulation. Several groups have demonstrated that in the mdx mouse, exon-skipping strategy can restore a quasi-dystrophin almost 100% of muscle fibers. On other hand, inhibition myostatin pathway adult mice has been described to enhance growth improve force. Our aim was combine these two strategies evaluate possible additive effect. We chosen inhibit using technique RNA interference directed against receptor AcvRIIb...
Aging is associated with a progressive loss of muscle mass, increased adiposity and fibrosis that leads to sarcopenia. At the molecular level, aging known alter expression variety genes but very little about effectors involved. SRF (Serum Response Factor) crucial transcription factor for muscle-specific gene post-natal skeletal growth. To assess its role in adult physiology, we developed post-mitotic myofiber-specific tamoxifen-inducible knockout model. Five months after loss, no obvious...