Muscular dystrophies, myopathies, inherited peripheral neuropathies and hereditary ataxias groups of diseases studied by the team are part of the large family of neuromuscular disorders (NMD), a set of hereditary diseases ultimately leading to muscle dysfunction, due to muscle or nerve abnormalities. Although quite different in terms of affected genes and pathways, these diseases are defined by a strong genetic heterogeneity leading to complex physiopathological pathways. Improving diagnosis of these diseases, the understanding of the pathomechanisms and defining new treatments are primary goals that we want to achieve.

Group leader: Martin Krahn

The research group “Translational Genomics” will constitute the genomics resource of the team, and coordinate translational research projects focused on the applicative development of novel genome analysis technologies, with the aim of improving genetic diagnosis in clinical applications, and novel gene identification. Efforts will be made specifically to further increase diagnostic yields and validate the implication of novel genes in neuromuscular diseases through (i) the adaption of Whole-exome and Whole-genome Next Generation Sequencing (NGS), and (ii) the development of functional tests for the characterization of the pathogenic impact of sequence variants, the latter points will be enriched and positioned in a highly propitious research environment through the close collaborations with the group lead by Pr. C. Béroud (Bioinformatics and genetics), the group led by Dr. F. Magdinier (Epigenetics, Chromatin & Disease modeling), and the newly created genomics platform of our Research Unit headed by Dr. V. Delague.

The “Translational Genomics” relays on our expertise acquired in this field during the past 8 years, in particular through our participation to four FP7 European Projects (NMD-CHIP, BIO-NMD  and NEUROMICS), the MYOCAPTURE project,  Moreover, this group is closely linked to the diagnostic activities and the constitution of large national and international cohorts within the Department of Medical Genetics of Marseille (Hôpital d’Enfants de La Timone; Assistance Publique - Hôpitaux de Marseille), in strong relationship with the Reference Center for Neuromuscular Diseases and Lateral Amyotrophic Sclerosis in Marseille (Pr. J. Pouget and Pr. S. Attarian). Noteworthy, for different types of neuromuscular diseases on which our “NMD Department” focuses (i.e. Dysferlinopathies, Calpainopathies, GNEpathies, FSHD, Channelopathies), the Department of Medical Genetics of Marseille is the national French reference laboratory for genetic diagnosis, receiving the large majority of patient samples throughout France.


Group leader: Valérie Delague

Inherited peripheral neuropathies (IPN) are one of the most frequent inherited causes of neurological disability characterized by extensive phenotypic and genetic heterogeneity. This group of neuromuscular disorders is distinguished by length-dependent progressive degeneration of the PNS. Based on clinical and electrophysiological properties, they can be subdivided into three main groups: Hereditary Motor and sensory Neuropathies (HMSN), also known as Charcot-Marie-Tooth disease (CMT), pure motor neuropathies (distal Hereditary Motor Neuropathies, abbreviated dHMN) and pure sensitive neuropathies (Hereditary Sensory Neuropathies, abbreviated HSN). Among IPN, CMT is the most common inherited disorder of the human peripheral nerve with a prevalence of 1 in 2500.

Our research group is dedicated toward unraveling the missing keys in genetics and physiopathology of Inherited Peripheral Neuropathies (IPNs) (mostly Charcot-Marie-Tooth disease (CMT)), in order to improve diagnosis and to set-up therapeutic strategies. This group of neuromuscular diseases is characterized by a strong genetic heterogeneity, with about 80 genes identified to date and all modes of inheritance described. These genes encode proteins of various functions in both axon and myelin. Beyond the major importance of gene identification in IPN in molecular diagnosis and genetic counselling of families affected with these diseases, the identification of defective genes in IPN is a major stimulus toward understanding the role of normal and mutant proteins in peripheral nerve, and in consequence the biology of myelin. These genes can be viewed as the result of a functional screen revealing crucial players in the interactions between Schwann cell and neurons. Studying how Schwann cell and axon-encoded proteins are functionally interconnected will provide crucial information about the interplay between SC and neurons. Moreover, comprehension of these processes is also crucial to identify targets for therapeutic interventions. In this context, we have several axes of research :

1)            Identify new genes in IPN/CMT by studying large consanguineous families affected with rare autosomal recessive forms using a combination of homozygosity mapping and Next-Generation Sequencing (WGS/WES) and realize subsequent functional studies.

2)            Understand the physiopathology of some CMT subtypes, in particular CMT4H, a rare autosomal recessive demyelinating form of Charcot-Marie-Tooth disease, for which we have described FGD4 as the culprit gene in 2007, using both cellular and animal models (mouse, zebrafish).

3) Develop a new human induced Pluripotent Stem Cells (hiPSC)-based in vitro model for the peripheral nerve system, in order both to assess the pathogenicity of the mutations identified in the genetic studies, and to dispose of a new tool for functional and preclinical therapeutic studies.



Group leader: Marc Bartoli

Using innovative approaches, we will identify new defective genes/proteins in NMD diseases. This group “Biotherapies Targeted to Neuromuscular Disorders” will focus on the comprehension of the pathomechanisms underlying the diseases caused by these new mutations/disease genes. The objectives here are to pave the way for the development of new therapies, by i) studying the physiopathological mechanisms underlying the studied diseases, due to mutations in new defective genes in NMD, or new mutations in genes already involved in other hereditary diseases (NMD or not); and ii) determining the interactions between these proteins in normal and pathological conditions. Identifying new players in NMD diseases is of major importance, not only for molecular diagnosis and genetic counselling of families affected with these diseases, but also toward understanding the role of normal and mutant proteins in muscle. These genes can be viewed as the result of a functional screen revealing crucial players in the biology of muscles, the interaction between muscle and neurons.

For years, neuromuscular disorders have been considered as incurable diseases, however for fifteen years several proof of concept (PoC) have emerged and rise new hope for patients. The research group “Biotherapies targeted to neuromuscular disorders “, directed by Marc Bartoli aims to develop innovative therapeutic approaches for different neuromuscular diseases. The “Biotherapies targeted to neuromuscular disorders” group rely on a strong expertise obtained during the past years, in particular M. Bartoli contributed in the establishment of seven PoC that demonstrate the feasibility of several approaches for three distinct neuromuscular diseases and participated in clinical trials. This group will be closely linked to activities of the two other groups constituting the NeuroMyology team in particular by valorizing studies of patients presenting with extreme phenotype.

In particular, we develop novel therapeutic approaches, based on particular clinical observations and mutational data from our large cohort of patients. We will pursue our previous work towards further preclinical testing of therapeutic strategies developed by our group in particular: transcript rescue strategies (Exon skipping/Trans-splicing…).   

Besides these transcript rescue strategies, we will also develop gene transfer strategy. We also advance “classical” pharmaceutical therapeutic approaches to neuromuscular diseases, under the condition that pharmaceutical targets are identified based on the molecular pathophysiology.
Finally, we intend to define the best strategy using preclinical models to assay efficacy of considered approaches to alleviate neuromuscular diseases. Ultimately, if some approaches are successful, they may lead towards translational strategies and we will further establish partnerships at national and international level, to accelerate implementation of innovation. We will make sure that the process of design, development and validation of our therapeutic strategies will go through a process of clinical trial evaluation. This part of the project represents a strategic decision for the team with the objective of introducing the knowledge and collaborations for the translation of our pre-clinical research projects into the development of clinical trials. In this context, we envisaged to participate in clinical trials promoted by biotech/pharmacological companies before launching our own clinical trials.


Warnez-Soulie, J.  et al. 2019

Tumor protein 53-induced nuclear protein 1 deficiency alters mouse gastrocnemius muscle function and bioenergetics in vivo

Tumor protein 53-induced nuclear protein 1 (TP53INP1) deficiency leads to oxidative stress-associated obesity and insulin resistance. Although skeletal muscle has a predominant role in the development...
Physiol Rep - issue: 10 - volume: 7 - pages: e14055.

Dominov, JA.  et al. 2019

Correction of pseudoexon splicing caused by a novel intronic dysferlin mutation

Objective Dysferlin is a large transmembrane protein that functions in critical processes of membrane repair and vesicle fusion. Dysferlin-deficiency due to mutations in the dysferlin gene leads to...
Ann. Clin. Transl. Neurol. - issue: 4 - volume: 6 - pages: 642-654.

Barthélémy, F.  et al. 2018

Dysferlin Exon 32 Skipping in Patient Cells

Dysferlinopathies are rare genetic diseases affecting muscles due to mutations in DYSF. Exon 32 of DYSF has been shown to be dispensable for dysferlin functions. Here we present a method to visualize...
Methods Mol. Biol. - issue: - volume: 1828 - pages: 489-496.

Desvignes, J.  et al. 2018

VarAFT: a variant annotation and filtration system for human next generation sequencing data

With the rapidly developing high-throughput sequencing technologies known as next generation sequencing or NGS, our approach to gene hunting and diagnosis has drastically changed. In <10 years, these...
Nucleic Acids Res. - issue: W1 - volume: 46 - pages: W545-W553.

Nguyen, K.  et al. 2017

Molecular combing reveals complex 4q35 rearrangements in Facioscapulohumeral dystrophy

Facioscapulohumeral dystrophy (FSHD), one of the most common hereditary neuromuscular disorders, is associated with a complex combination of genetic variations at the subtelomeric 4q35 locus. As...
Hum. Mutat. - issue: 10 - volume: 38 - pages: 1432-1441.

Cerino, M.  et al. 2017

Genetic Characterization of a French Cohort of GNE-mutation negative inclusion body myopathy patients with exome sequencing

INTRODUCTION: Hereditary inclusion body myopathy (hIBM) refers to a group of clinically and genetically heterogeneous diseases. The overlapping histochemical features of hIBM with other genetic...
Muscle Nerve - issue: - volume: - pages: .

Matagne, V.  et al. 2016

A codon-optimized Mecp2 transgene corrects breathing deficits and improves survival in a mouse model of Rett syndrome

Rett syndrome (RTT) is a severe X-linked neurodevelopmental disorder that is primarily caused by mutations in the methyl CpG binding protein 2 gene (MECP2). RTT is the second most prevalent cause of...
Neurobiol. Dis. - issue: - volume: 99 - pages: 1-11.

Gaillard, M.  et al. 2016

Segregation between SMCHD1 mutation, D4Z4 hypomethylation and Facio-Scapulo-Humeral Dystrophy: a case report

BACKGROUND: The main form of Facio-Scapulo-Humeral muscular Dystrophy is linked to copy number reduction of the 4q D4Z4 macrosatellite (FSHD1). In 5 % of cases, FSHD phenotype appears in the absence...
BMC Med. Genet. - issue: 1 - volume: 17 - pages: 66.

Sevy, A.  et al. 2016

Improving molecular diagnosis of distal myopathies by targeted next-generation sequencing

J. Neurol. Neurosurg. Psychiatry - issue: 3 - volume: 87 - pages: 340-U116.

Gorokhova, S.  et al. 2015

Comparing targeted exome and whole exome approaches for genetic diagnosis of neuromuscular disorders

Massively parallel sequencing is rapidly becoming a widely used method in genetic diagnostics. However, there is still no clear consensus as to which approach can most efficiently identify the...
Appl. Transl. Genomics - issue: - volume: 7 - pages: 26-31.

Martinez, E.  et al. 2015

Rs488087 single nucleotide polymorphism as predictive risk factor for pancreatic cancers

Pancreatic cancer (PC) is a devastating disease progressing asymptomatically until death within months after diagnosis. Defining at-risk populations should promote its earlier diagnosis and hence also...
Oncotarget - issue: 37 - volume: 6 - pages: 39855-39864.

Barthélémy, F.  et al. 2015

Exon 32 Skipping of Dysferlin Rescues Membrane Repair in Patients' Cells

Dysferlinopathies are a family of disabling muscular dystrophies with LGMD2B and Miyoshi myopathy as the main phenotypes. They are associated with molecular defects in DYSF, which encodes dysferlin, a...
J Neuromuscul Dis - issue: 3 - volume: 2 - pages: 281-290.

Mariot, V.  et al. 2015

Correlation between low FAT1 expression and early affected muscle in facioscapulohumeral muscular dystrophy

OBJECTIVE: Facioscapulohumeral muscular dystrophy (FSHD) is linked to either contraction of D4Z4 repeats on chromosome 4 or to mutations in the SMCHD1 gene, both of which result in the aberrant...
Ann. Neurol. - issue: 3 - volume: 78 - pages: 387-400.

Barthélémy, F.  et al. 2015

Truncated prelamin A expression in HGPS-like patients: a transcriptional study

Premature aging syndromes are rare genetic disorders mimicking clinical and molecular features of aging. A recently identified group of premature aging syndromes is linked to mutation of the LMNA gene...
Eur. J. Hum. Genet. - issue: 8 - volume: 23 - pages: 1051-1061.

Kergourlay, V.  et al. 2015

Comment on: A novel dysferlin-mutant pseudoexon bypassed with antisense oligonucleotides

Ann Clin Transl Neurol - issue: 7 - volume: 2 - pages: 783-784.

Gorokhova, S.  et al. 2015

Clinical massively parallel sequencing for the diagnosis of myopathies

Massively parallel sequencing, otherwise known as high-throughput or next-generation sequencing, is rapidly gaining wide use in clinical practice due to possibility of simultaneous exploration of...
Rev. Neurol. (Paris) - issue: 6-7 - volume: 171 - pages: 558-571.

Cerino, M.  et al. 2015

Novel Pathogenic Variants in a French Cohort Widen the Mutational Spectrum of GNE Myopathy

BACKGROUND: GNE myopathy is a rare autosomal recessively inherited muscle disease resulting from mutations in the gene encoding GNE (UDP-N-acetylglucosamine-2-epimerase/N-acetylmannosamine kinase), a...
J Neuromuscul Dis - issue: 2 - volume: 2 - pages: 131-136.

Puppo, F.  et al. 2015

Identification of variants in the 4q35 gene FAT1 in patients with a facioscapulohumeral dystrophy-like phenotype

Facioscapulohumeralmuscular dystrophy (FSHD) is linked to copy-number reduction (N < 10) of the 4q D4Z4 subtelomeric array, in association with DUX4-permissive haplotypes. This main form is indicated...
Hum. Mutat. - issue: 4 - volume: 36 - pages: 443-453.

Salort-Campana, E.  et al. 2015

Low penetrance in facioscapulohumeral muscular dystrophy type 1 with large pathological D4Z4 alleles: a cross-sectional multicenter study

BACKGROUND: Facioscapulohumeral muscular dystrophy type 1(FSHD1) is an autosomal dominant disorder associated with the contraction of D4Z4 less than 11 repeat units (RUs) on chromosome 4q35....
Orphanet J Rare Dis - issue: - volume: 10 - pages: 2.

Bartoli, M.  et al. 2014

Exome sequencing as a second-tier diagnostic approach for clinically suspected dysferlinopathy patients

INTRODUCTION: Autosomal recessive muscular dystrophies are heterogeneous genetic disorders, with 39 genes currently implicated. Genetic diagnosis using targeted single-gene analysis by Sanger...
Muscle Nerve - issue: 6 - volume: 50 - pages: 1007-1010.

Kergourlay, V.  et al. 2014

Identification of splicing defects caused by mutations in the dysferlin gene

Missense, iso-semantic, and intronic mutations are challenging for interpretation, in particular for their impact in mRNA. Various tools such as the Human Splicing Finder (HSF) system could be used to...
Hum. Mutat. - issue: 12 - volume: 35 - pages: 1532-1541.

Puppo, F.  et al. 2014

Molecular defects in FAT1 are associated to facioscapulohumeral dystrophy (FSHD)

Neuromusc. Disord. - issue: 9-10 - volume: 24 - pages: 797-798.

Jaka, O.  et al. 2014

Entire CAPN3 gene deletion in a patient with limb-girdle muscular dystrophy type 2A

Limb-girdle muscular dystrophy type 2A (LGMD2A) due to mutations in the CAPN3 gene is one of the most common of autosomal recessive limb-girdle muscular dystrophies. We describe a patient who had a...
Muscle Nerve - issue: 3 - volume: 50 - pages: 448-453.

Gaillard, M.  et al. 2014

Differential DNA methylation of the D4Z4 repeat in patients with FSHD and asymptomatic carriers

OBJECTIVE: We investigated the link between DNA hypomethylation and clinical penetrance in facioscapulohumeral dystrophy (FSHD) because hypomethylation is moderate and heterogeneous in patients and...
Neurology - issue: 8 - volume: 83 - pages: 733-742.

Broucqsault, N.  et al. 2013

Dysregulation of 4q35- and muscle-specific genes in fetuses with a short D4Z4 array linked to facio-scapulo-humeral dystrophy

Facio-scapulo-humeral dystrophy (FSHD) results from deletions in the subtelomeric macrosatellite D4Z4 array on the 4q35 region. Upregulation of the DUX4 retrogene from the last D4Z4 repeated unit is...
Hum. Mol. Genet. - issue: 20 - volume: 22 - pages: 4206-4214.

Roudaut, C.  et al. 2013

Restriction of calpain3 expression to the skeletal muscle prevents cardiac toxicity and corrects pathology in a murine model of limb-girdle muscular dystrophy

BACKGROUND: Genetic defects in calpain3 (CAPN3) lead to limb-girdle muscular dystrophy type 2A, a disease of the skeletal muscle that affects predominantly the proximal limb muscles. We previously...
Circulation - issue: 10 - volume: 128 - pages: 1094-1104.

Caruso, N.  et al. 2013

Deregulation of the protocadherin gene FAT1 alters muscle shapes: implications for the pathogenesis of facioscapulohumeral dystrophy

Generation of skeletal muscles with forms adapted to their function is essential for normal movement. Muscle shape is patterned by the coordinated polarity of collectively migrating myoblasts....
PLoS Genet. - issue: 6 - volume: 9 - pages: e1003550.

Blandin, G.  et al. 2013

A human skeletal muscle interactome centered on proteins involved in muscular dystrophies: LGMD interactome

BACKGROUND: The complexity of the skeletal muscle and the identification of numerous human disease-causing mutations in its constitutive proteins make it an interesting tissue for proteomic studies...
Skelet Muscle - issue: 1 - volume: 3 - pages: 3.

Boehm, J.  et al. 2013

Constitutive Activation of the Calcium Sensor STIM1 Causes Tubular-Aggregate Myopathy

Tubular aggregates are regular arrays of membrane tubules accumulating in muscle with age. They are found as secondary features in several muscle disorders, including alcohol- and drug-induced...
Am. J. Hum. Genet. - issue: 2 - volume: 92 - pages: 271-278.

Lostal, W.  et al. 2012

Lack of correlation between outcomes of membrane repair assay and correction of dystrophic changes in experimental therapeutic strategy in dysferlinopathy

Mutations in the dysferlin gene are the cause of Limb-girdle Muscular Dystrophy type 2B and Miyoshi Myopathy. The dysferlin protein has been implicated in sarcolemmal resealing, leading to the idea...
PLoS ONE - issue: 5 - volume: 7 - pages: e38036.

De Paula, AM.  et al. 2012

Further heterogeneity in myopathy with tubular aggregates?

Muscle Nerve - issue: 6 - volume: 46 - pages: 984-985.

Eyrnard, B.  et al. 2012

Diagnostic strategy for limb-girdle muscular dystrophies

Limb-girdle muscular dystrophies represent a major chapter of genetic myopathies. Many different entities have been identified, most of them with recessive transmission, a minority with dominant...
Rev. Neurol. - issue: 12 - volume: 168 - pages: 919-926.

Blandin, G.  et al. 2012

UMD-DYSF, a novel locus specific database for the compilation and interactive analysis of mutations in the dysferlin gene

Mutations in the dysferlin gene (DYSF) lead to a complete or partial absence of the dysferlin protein in skeletal muscles and are at the origin of dysferlinopathies, a heterogeneous group of rare...
Hum. Mutat. - issue: 3 - volume: 33 - pages: E2317-2331.

Soheili, T.  et al. 2012

Rescue of sarcoglycan mutations by inhibition of endoplasmic reticulum quality control is associated with minimal structural modifications

Sarcoglycanopathies (SGP) are a group of autosomal recessive muscle disorders caused by primary mutations in one of the four sarcoglycan genes. The sarcoglycans (α-, β-, γ-, and δ-sarcoglycan) form a...
Hum. Mutat. - issue: 2 - volume: 33 - pages: 429-439.

Bartoli, M.  et al. 2012

Validation of comparative genomic hybridization arrays for the detection of genomic rearrangements of the calpain-3 and dysferlin genes

Clin. Genet. - issue: 1 - volume: 81 - pages: 99-101.

Krahn, M.  et al. 2011

Eosinophilic infiltration related to CAPN3 mutations: a pathophysiological component of primary calpainopathy?

Clin. Genet. - issue: 4 - volume: 80 - pages: 398-402.

Barthélémy, F.  et al. 2011

Translational research and therapeutic perspectives in dysferlinopathies

Dysferlinopathies are autosomal recessive disorders caused by mutations in the dysferlin (DYSF) gene, encoding the dysferlin protein. DYSF mutations lead to a wide range of muscular phenotypes, with...
Mol. Med. - issue: 9-10 - volume: 17 - pages: 875-882.

Laure, L.  et al. 2010

A new pathway encompassing calpain 3 and its newly identified substrate cardiac ankyrin repeat protein is involved in the regulation of the nuclear factor-kappa B pathway in skeletal muscle

A multiprotein complex encompassing a transcription regulator, cardiac ankyrin repeat protein ( CARP), and the calpain 3 protease was identified in the N2A elastic region of the giant sarcomeric...
FEBS J. - issue: 20 - volume: 277 - pages: 4322-4337.

Krahn, M.  et al. 2010

A naturally occurring human minidysferlin protein repairs sarcolemmal lesions in a mouse model of dysferlinopathy

Dysferlinopathies are autosomal recessive, progressive muscle dystrophies caused by mutations in DYSF, leading to a loss or a severe reduction of dysferlin, a key protein in sarcolemmal repair....
Sci Transl Med - issue: 50 - volume: 2 - pages: 50ra69.

Lévy, N.  et al. 2010

Therapeutic exon 'switching' for dysferlinopathies?

Eur. J. Hum. Genet. - issue: 9 - volume: 18 - pages: 969-970; author reply 971.

Lostal, W.  et al. 2010

Efficient recovery of dysferlin deficiency by dual adeno-associated vector-mediated gene transfer

Deficiency of the dysferlin protein presents as two major clinical phenotypes: limb-girdle muscular dystrophy type 2B and Miyoshi myopathy. Dysferlin is known to participate in membrane repair,...
Hum. Mol. Genet. - issue: 10 - volume: 19 - pages: 1897-1907.

Wein, N.  et al. 2010

Efficient bypass of mutations in dysferlin deficient patient cells by antisense-induced exon skipping

Mutations in DYSF encoding dysferlin cause primary dysferlinopathies, autosomal recessive diseases that mainly present clinically as Limb Girdle Muscular Dystrophy type 2B and Miyoshi myopathy. More...
Hum. Mutat. - issue: 2 - volume: 31 - pages: 136-142.

Krahn, M.  et al. 2010

Exclusion of mutations in the dysferlin alternative exons 1 of DYSF-v1, 5a, and 40a in a cohort of 26 patients

Mutations in the gene encoding dysferlin (DYSF; MIM# 603009, 2p13, GenBank NM_003494.2) cause primary dysferlinopathies, which are autosomal recessive muscular dystrophies. DYSF has a large mutational...
Genet Test Mol Biomarkers - issue: 1 - volume: 14 - pages: 153-154.

Mellgren, RL.  et al. 2009

Calcium-dependent plasma membrane repair requires m- or mu-calpain, but not calpain-3, the proteasome, or caspases

Mechanically damaged plasma membrane undergoes rapid calcium-dependent resealing that appears to depend, at least in part, on calpain-mediated cortical cytoskeletal remodeling. Cells null for Capns1,...
Biochim. Biophys. Acta - issue: 12 - volume: 1793 - pages: 1886-1893.

Laure, L.  et al. 2009

Cardiac ankyrin repeat protein is a marker of skeletal muscle pathological remodelling

In an attempt to identify potential therapeutic targets for the correction of muscle wasting, the gene expression of several pivotal proteins involved in protein metabolism was investigated in...
FEBS J. - issue: 3 - volume: 276 - pages: 669-684.

Bartoli, M.  et al. 2008

Mannosidase I inhibition rescues the human alpha-sarcoglycan R77C recurrent mutation

Limb girdle muscular dystrophy type 2D (LGMD2D, OMIM600119) is a genetic progressive myopathy that is caused by mutations in the human alpha-sarcoglycan gene (SGCA). Here, we have introduced in mice...
Hum. Mol. Genet. - issue: 9 - volume: 17 - pages: 1214-1221.

Benayoun, B.  et al. 2008

NF-kappa B-dependent expression of the antiapoptotic factor c-FLIP is regulated by calpain 3, the protein involved in limb-girdle muscular dystrophy type 2A

Limb-girdle muscular dystrophy type 2A (LGMD2A) is a recessive genetic disorder caused by mutations in the cysteine protease calpain 3 (CAPN3) that leads to selective muscle wasting. We previously...
Faseb J. - issue: 5 - volume: 22 - pages: 1521-1529.

Daniele, N.  et al. 2007

Ins and outs of therapy in limb girdle muscular dystrophies

Muscular dystrophies are hereditary degenerative muscle diseases that cause life-long disability in patients. They comprise the well-known Duchenne Muscular Dystrophy (DMD) but also the group of Limb...
Int. J. Biochem. Cell Biol. - issue: 9 - volume: 39 - pages: 1608-1624.

Bartoli, M.  et al. 2007

AAV-mediated delivery of a mutated myostatin propeptide ameliorates calpain 3 but not alpha-sarcoglycan deficiency

Myostatin is a negative regulator of muscle mass whose inhibition has been proposed as a therapeutic strategy for muscle-wasting conditions. Indeed, blocking myostatin action through different...
Gene Ther. - issue: 9 - volume: 14 - pages: 733-740.

Milic, A.  et al. 2007

A third of LGMD2A biopsies have normal calpain 3 proteolytic activity as determined by an in vitro assay

Limb-girdle muscular dystrophy type 2A (LGMD2A) is an autosomal recessive muscular disorder caused by mutations in the gene coding for calpain 3, a calcium-dependent protease. We developed an in vitro...
Neuromuscul. Disord. - issue: 2 - volume: 17 - pages: 148-156.

Fougerousse, F.  et al. 2007

Phenotypic correction of alpha-sarcoglycan deficiency by intra-arterial injection of a muscle-specific serotype 1 rAAV vector

alpha-Sarcoglycanopathy (limb-girdle muscular dystrophy type 2D, LGMD2D) is a recessive muscular disorder caused by deficiency in alpha-sarcoglycan, a transmembrane protein part of the...
Mol. Ther. - issue: 1 - volume: 15 - pages: 53-61.

Bartoli, M.  et al. 2006

A mouse model for monitoring calpain activity under physiological and pathological conditions

Calpains are Ca(2+)-dependent cysteine proteases known to be important for the regulation of cell functions and which aberrant activation causes cell death in a number of degenerative disorders. To...
J. Biol. Chem. - issue: 51 - volume: 281 - pages: 39672-39680.

Duguez, S.  et al. 2006

Calpain 3: a key regulator of the sarcomere?

Calpain 3 is a 94-kDa calcium-dependent cysteine protease mainly expressed in skeletal muscle. In this tissue, it localizes at several regions of the sarcomere through binding to the giant protein,...
FEBS J. - issue: 15 - volume: 273 - pages: 3427-3436.

Bartoli, M.  et al. 2006

Safety and efficacy of AAV-mediated calpain 3 gene transfer in a mouse model of limb-girdle muscular dystrophy type 2A

Calpainopathy (limb-girdle muscular dystrophy type 2A, LGMD2A) is a recessive muscular disorder caused by deficiency in the calcium-dependent cysteine protease calpain 3. To date, no treatment exists...
Mol. Ther. - issue: 2 - volume: 13 - pages: 250-259.

Bartoli, M.  et al. 2006

Noninvasive monitoring of therapeutic gene transfer in animal models of muscular dystrophies

Muscular dystrophies are a genetically and phenotypically heterogeneous group of degenerative muscle diseases. A subset of them are due to genetic deficiencies in proteins which form the...
Gene Ther. - issue: 1 - volume: 13 - pages: 20-28.

Bartoli, M.  et al. 2005

Calpains in muscle wasting

Calpains are intracellular nonlysosomal Ca(2+)-regulated cysteine proteases. They mediate regulatory cleavages of specific substrates in a large number of processes during the differentiation, life...
Int. J. Biochem. Cell Biol. - issue: 10 - volume: 37 - pages: 2115-2133.

Stockholm, D.  et al. 2005

Imaging calpain protease activity by multiphoton FRET in living mice

Constant efforts are ongoing for the development of new imaging methods that allow the investigation of molecular processes in vivo. Protein-protein interactions, enzymatic activities and...
J. Mol. Biol. - issue: 1 - volume: 346 - pages: 215-222.

Taveau, M.  et al. 2003

Calpain 3 is activated through autolysis within the active site and lyses sarcomeric and sarcolemmal components

Calpain 3 (Capn3) is known as the skeletal muscle-specific member of the calpains, a family of intracellular nonlysosomal cysteine proteases. This enigmatic protease has many unique features among the...
Mol. Cell. Biol. - issue: 24 - volume: 23 - pages: 9127-9135.

Gaillard, S.  et al. 2001

Striatin, a calmodulin-dependent scaffolding protein, directly binds caveolin-1

Caveolins are scaffolding proteins able to collect on caveolae a large number of signalling proteins bearing a caveolin-binding motif. The proteins of the striatin family, striatin, SG2NA, and...
FEBS Lett. - issue: 1 - volume: 508 - pages: 49-52.

Bartoli, M.  et al. 2001

Interactions of the rapsyn RING-H2 domain with dystroglycan

Rapsyn, a peripheral membrane protein of skeletal muscle, is necessary for the formation of the highly organized structure of the vertebrate neuromuscular junction. For mice lacking rapsyn, there is a...
J. Biol. Chem. - issue: 27 - volume: 276 - pages: 24911-24917.

Bartoli, M.  et al. 1999

Down-regulation of striatin, a neuronal calmodulin-binding protein, impairs rat locomotor activity

Striatin, an intraneuronal, calmodulin-binding protein addressed to dendrites and spines, is expressed in the motor system, particularly the striatum and motoneurons. Striatin contains a high number...
J. Neurobiol. - issue: 2 - volume: 40 - pages: 234-243.

Bartoli, M.  et al. 1998

Interaction of calmodulin with striatin, a WD-repeat protein present in neuronal dendritic spines

Rat striatin, a quantitatively minor protein belonging to the WD-repeat family of proteins, is a Ca2+/calmodulin-binding protein mostly expressed in the striatum and in the motor and olfactory systems...
J. Biol. Chem. - issue: 35 - volume: 273 - pages: 22248-22253.

Salin, P.  et al. 1998

Distribution of striatin, a newly identified calmodulin-binding protein in the rat brain: an in situ hybridization and immunocytochemical study

Striatin, a 110-kDa protein, is the first member of the tryptophane-aspartate repeat protein family known to bind calmodulin in the presence of Ca2+. We examined the distribution of striatin and its...
J. Comp. Neurol. - issue: 1 - volume: 397 - pages: 41-59.

Moqrich, A.  et al. 1998

Cloning of human striatin cDNA (STRN), gene mapping to 2p22-p21, and preferential expression in brain

Rat striatin, a recently discovered calmodulin-binding protein belonging to the WD repeat family, is expressed in neurons, mostly in the striatum and motor and olfactory systems. Striatin is localized...
Genomics - issue: 1 - volume: 51 - pages: 136-139.

Kachidian, P.  et al. 1998

Relationships between striatin-containing neurons and cortical or thalamic afferent fibres in the rat striatum. An ultrastructural study by dual labelling

Striatin, a recently isolated rat brain calmodulin-binding protein belonging to the WD-repeat protein family, is thought to be part of a calcium signal transduction pathway presumably specific to...
Neuroscience - issue: 1 - volume: 85 - pages: 111-122.

Castets, F.  et al. 1996

A novel calmodulin-binding protein, belonging to the WD-repeat family, is localized in dendrites of a subset of CNS neurons

A rat brain synaptosomal protein of 110,000 M(r) present in a fraction highly enriched in adenylyl cyclase activity was microsequenced (Castets, F., G. Baillat, S. Mirzoeva, K. Mabrouk, J. Garin, J....
J. Cell Biol. - issue: 4 - volume: 134 - pages: 1051-1062.