Search

Your search keyword '"Christine Kretz"' showing total 12 results
Start Over Author "Christine Kretz" Publisher hal ccsd
12 results on '"Christine Kretz"'

1. Differential physiological role of BIN1 isoforms in skeletal muscle development, function and regeneration

Author

Vincent Gache, Arnaud Ferry, Fanny Pilot-Storck, Olivia Wendling, Vincent Jacquemond, Vasugi Nattarayan, Jeanne Lainé, Jocelyn Laporte, Christine Kretz, Hichem Tasfaout, Roy Combe, Josiane Hergueux, Anne Toussaint, Christos Gavriilidis, Catherine Koch, Belinda S. Cowling, Candice Kutchukian, Ivana Prokic, Laurent Tiret, Institut de Génétique et de Biologie Moléculaire et Cellulaire (IGBMC), Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Institut NeuroMyoGène (INMG), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Centre de recherche en Myologie – U974 SU-INSERM, Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Institut Clinique de la Souris (ICS), Biologie du système neuromusculaire - Biology of the neuromuscular system [Maisons-Alfort] (BNMS - Team 10), École nationale vétérinaire - Alfort (ENVA)-Institut Mondor de Recherche Biomédicale (IMRB), Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12)-Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut de Myologie, Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Association française contre les myopathies (AFM-Téléthon)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Strasbourg (UNISTRA), École nationale vétérinaire d'Alfort (ENVA)-Institut Mondor de Recherche Biomédicale (IMRB), Centre National de la Recherche Scientifique (CNRS)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Association française contre les myopathies (AFM-Téléthon)-Sorbonne Université (SU), Centre de Recherche en Myologie, Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12)-IFR10-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12)-IFR10, Gestionnaire, HAL Sorbonne Université 5, BLANC - Mécano-sensation et mécano-stabilisation au cours de la morphogenèse embryonnaire - - SenStable2011 - ANR-11-BSV2-0023 - BLANC - VALID, ANR-11-BSV2-0023,SenStable,Mécano-sensation et mécano-stabilisation au cours de la morphogenèse embryonnaire(2011), and Université de Lyon

Subjects
XLMTM, [SDV]Life Sciences [q-bio], Muscle Fibers, Skeletal, lcsh:Medicine, Medicine (miscellaneous), Muscle Development, centronuclear myopathy, SH3 domain, Myoblast fusion, 0302 clinical medicine, Immunology and Microbiology (miscellaneous), myoblast fusion, Protein Isoforms, myotubular myopathy, ComputingMilieux_MISCELLANEOUS, Sequence Deletion, 0303 health sciences, triad, Homozygote, Exons, Cell biology, medicine.anatomical_structure, Organ Specificity, Knockout mouse, Intracellular, Research Article, lcsh:RB1-214, Gene isoform, Neuroscience (miscellaneous), Nerve Tissue Proteins, Biology, General Biochemistry, Genetics and Molecular Biology, 03 medical and health sciences, dynamin, lcsh:Pathology, [SDV.BBM] Life Sciences [q-bio]/Biochemistry, Molecular Biology, medicine, Animals, Regeneration, [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology, Centronuclear myopathy, Muscle, Skeletal, Adaptor Proteins, Signal Transducing, 030304 developmental biology, Dynamin, myotonic dystrophy, Tumor Suppressor Proteins, Regeneration (biology), animal model, lcsh:R, Skeletal muscle, Feeding Behavior, medicine.disease, Survival Analysis, Mice, Inbred C57BL, Animals, Newborn, BAR domain, 030217 neurology & neurosurgery
Abstract

Skeletal muscle development and regeneration are tightly regulated processes. How the intracellular organization of muscle fibers is achieved during these steps is unclear. Here, we focus on the cellular and physiological roles of amphiphysin 2 (BIN1), a membrane remodeling protein mutated in both congenital and adult centronuclear myopathies (CNM), that is ubiquitously expressed and has skeletal muscle-specific isoforms. We created and characterized constitutive muscle-specific and inducible Bin1 homozygous and heterozygous knockout mice targeting either ubiquitous or muscle-specific isoforms. Constitutive Bin1-deficient mice died at birth from lack of feeding due to a skeletal muscle defect. T-tubules and other organelles were misplaced and altered, supporting a general early role for BIN1 in intracellular organization, in addition to membrane remodeling. Although restricted deletion of Bin1 in unchallenged adult muscles had no impact, the forced switch from the muscle-specific isoforms to the ubiquitous isoforms through deletion of the in-frame muscle-specific exon delayed muscle regeneration. Thus, ubiquitous BIN1 function is necessary for muscle development and function, whereas its muscle-specific isoforms fine tune muscle regeneration in adulthood, supporting that BIN1 CNM with congenital onset are due to developmental defects, whereas later onset may be due to regeneration defects., Summary: The BIN1 gene, mutated in centronuclear myopathies, expresses ubiquitous and muscle-specific isoforms. It is shown here that ubiquitous isoforms are necessary for muscle development, whereas muscle-specific isoforms fine-tune muscle regeneration.

Published
2020
Full Text
View/download PDF

2. Amphiphysin 2 modulation rescues myotubular myopathy and prevents focal adhesion defects in mice

Author

Maxime Sartori, Valentina M. Lionello, Christine Kretz, Nadia Messaddeq, Jocelyn Laporte, Yann Herault, Pascale Koebel, Sarah Djerroud, Belinda S. Cowling, Suzie Buono, Anne-Sophie Nicot, Pascal Kessler, Ivana Prokic, Norma B. Romero, Institut de génétique et biologie moléculaire et cellulaire (IGBMC), Université Louis Pasteur - Strasbourg I-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Laboratoire de neurosciences cognitives et adaptatives (LNCA), Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS), Institut de Génétique et de Biologie Moléculaire et Cellulaire (IGBMC), Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Institut de Myologie, Université Pierre et Marie Curie - Paris 6 (UPMC)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Association française contre les myopathies (AFM-Téléthon)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), IGBMC-Médecine translationnelle et neurogénétique, Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA), Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Association française contre les myopathies (AFM-Téléthon)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Pierre et Marie Curie - Paris 6 (UPMC), and Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)

Subjects
Male, Myotubularin, Integrin, Longevity, Mice, Transgenic, Nerve Tissue Proteins, Focal adhesion, 03 medical and health sciences, 0302 clinical medicine, Laminin, medicine, Myocyte, Animals, Humans, Muscle Strength, ComputingMilieux_MISCELLANEOUS, 030304 developmental biology, Adaptor Proteins, Signal Transducing, 0303 health sciences, Focal Adhesions, [SDV.GEN]Life Sciences [q-bio]/Genetics, biology, Integrin beta1, Muscles, Tumor Suppressor Proteins, Skeletal muscle, Muscle weakness, Nuclear Proteins, General Medicine, Protein Tyrosine Phosphatases, Non-Receptor, 3. Good health, Cell biology, medicine.anatomical_structure, Animals, Newborn, Amphiphysin, biology.protein, medicine.symptom, 030217 neurology & neurosurgery, Myopathies, Structural, Congenital
Abstract

Centronuclear myopathies (CNMs) are severe diseases characterized by muscle weakness and myofiber atrophy. Currently, there are no approved treatments for these disorders. Mutations in the phosphoinositide 3-phosphatase myotubularin (MTM1) are responsible for X-linked CNM (XLCNM), also called myotubular myopathy, whereas mutations in the membrane remodeling Bin/amphiphysin/Rvs protein amphiphysin 2 [bridging integrator 1 (BIN1)] are responsible for an autosomal form of the disease. Here, we investigated the functional relationship between MTM1 and BIN1 in healthy skeletal muscle and in the physiopathology of CNM. Genetic overexpression of human BIN1 efficiently rescued the muscle weakness and life span in a mouse model of XLCNM. Exogenous human BIN1 expression with adeno-associated virus after birth also prevented the progression of the disease, suggesting that human BIN1 overexpression can compensate for the lack of MTM1 expression in this mouse model. Our results showed that MTM1 controls cell adhesion and integrin localization in mammalian muscle. Alterations in this pathway in Mtm1 −/y mice were associated with defects in myofiber shape and size. BIN1 expression rescued integrin and laminin alterations and restored myofiber integrity, supporting the idea that MTM1 and BIN1 are functionally linked and necessary for focal adhesions in skeletal muscle. The results suggest that BIN1 modulation might be an effective strategy for treating XLCNM.

Published
2019
Full Text
View/download PDF

3. Single Intramuscular Injection of AAV-shRNA Reduces DNM2 and Prevents Myotubular Myopathy in Mice

Author

Belinda S. Cowling, Jocelyn Laporte, Deborah Bitz, Pascale Koebel, Hichem Tasfaout, Nadia Messaddeq, Christine Kretz, Valentina M. Lionello, Institut de Génétique et de Biologie Moléculaire et Cellulaire (IGBMC), Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), French National Infrastructure for Mouse Phenogenomics (PHENOMIN), Institut Clinique de la Souris, and univOAK, Archive ouverte

Subjects
0301 basic medicine, Male, XLMTM, Myotubularin, [CHIM.THER]Chemical Sciences/Medicinal Chemistry, centronuclear myopathy, Small hairpin RNA, Dynamin II, Mice, shRNA, Drug Discovery, congenital myopathy, RNA, Small Interfering, Mice, Knockout, Gene knockdown, AAV, Dependovirus, Immunohistochemistry, 3. Good health, myotubularin, Phenotype, Treatment Outcome, Gene Knockdown Techniques, Molecular Medicine, Original Article, RNA Interference, medicine.symptom, Myopathies, Structural, Congenital, MTM1, [CHIM.THER] Chemical Sciences/Medicinal Chemistry, Genetic Vectors, Muscle disorder, Injections, Intramuscular, 03 medical and health sciences, dynamin, Genetics, medicine, Animals, RNA, Messenger, Centronuclear myopathy, Myopathy, Muscle, Skeletal, Molecular Biology, Pharmacology, business.industry, Muscle weakness, X-linked myotubular myopathy, Genetic Therapy, DNM2, medicine.disease, Disease Models, Animal, 030104 developmental biology, Cancer research, business
Abstract

Myotubular myopathy, or X-linked centronuclear myopathy, is a severe muscle disorder representing a significant burden for patients and their families. It is clinically characterized by neonatal and severe muscle weakness and atrophy. Mutations in the myotubularin (MTM1) gene cause myotubular myopathy, and no specific curative treatment is available. We previously found that dynamin 2 (DNM2) is upregulated in both Mtm1 knockout and patient muscle samples, whereas its reduction through antisense oligonucleotides rescues the clinical and histopathological features of this myopathy in mice. Here, we propose a novel approach targeting Dnm2 mRNA. We screened and validated in vitro and in vivo several short hairpin RNA (shRNA) sequences that efficiently target Dnm2 mRNA. A single intramuscular injection of AAV-shDnm2 resulted in long-term reduction of DNM2 protein level and restored muscle force, mass, histology, and myofiber ultrastructure and prevented molecular defects linked to the disease. Our results demonstrate a robust DNM2 knockdown and provide an alternative strategy based on reduction of DNM2 to treat myotubular myopathy.

Published
2018
Full Text
View/download PDF

4. Amphiphysin (BIN1) negatively regulates dynamin 2 for normal muscle maturation

Author

Aurélien Roux, Ivana Prokic, Belinda S. Cowling, Frédéric Humbert, Anne-Sophie Nicot, Hichem Tasfaout, Christine Kretz, Bruno Rinaldi, Aymen Rabai, Jocelyn Laporte, Sylvie Friant, IGBMC-Médecine translationnelle et neurogénétique, Institut de Génétique et de Biologie Moléculaire et Cellulaire (IGBMC), Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Génétique moléculaire, génomique, microbiologie (GMGM), Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS), Institut de génétique et biologie moléculaire et cellulaire (IGBMC), Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Louis Pasteur - Strasbourg I, Biochemistry Department - University of Geneva, and University of Geneva [Switzerland]

Subjects
0301 basic medicine, Gene isoform, Muscle Fibers, Skeletal, Nerve Tissue Proteins, [SDV.BC]Life Sciences [q-bio]/Cellular Biology, Biology, Dynamin II, Mice, 03 medical and health sciences, 0302 clinical medicine, In vivo, medicine, Animals, Protein Isoforms, Adaptor Proteins, Signal Transducing, Dynamin, Mice, Knockout, [SDV.GEN]Life Sciences [q-bio]/Genetics, Tumor Suppressor Proteins, Skeletal muscle, General Medicine, medicine.disease, In vitro, Cell biology, 030104 developmental biology, medicine.anatomical_structure, [SDV.GEN.GH]Life Sciences [q-bio]/Genetics/Human genetics, Amphiphysin, Alzheimer's disease, 030217 neurology & neurosurgery, Intracellular, Research Article, Myopathies, Structural, Congenital
Abstract

International audience; Regulation of skeletal muscle development and organization is a complex process that is not fully understood. Here, we focused on amphiphysin 2 (BIN1, also known as bridging integrator-1) and dynamin 2 (DNM2), two ubiquitous proteins implicated in membrane remodeling and mutated in centronuclear myopathies (CNMs). We generated Bin1-/- Dnm2+/- mice to decipher the physiological interplay between BIN1 and DNM2. While Bin1-/- mice die perinatally from a skeletal muscle defect, Bin1-/- Dnm2+/- mice survived at least 18 months, and had normal muscle force and intracellular organization of muscle fibers, supporting BIN1 as a negative regulator of DNM2. We next characterized muscle-specific isoforms of BIN1 and DNM2. While BIN1 colocalized with and partially inhibited DNM2 activity during muscle maturation, BIN1 had no effect on the isoform of DNM2 found in adult muscle. Together, these results indicate that BIN1 and DNM2 regulate muscle development and organization, function through a common pathway, and define BIN1 as a negative regulator of DNM2 in vitro and in vivo during muscle maturation. Our data suggest that DNM2 modulation has potential as a therapeutic approach for patients with CNM and BIN1 defects. As BIN1 is implicated in cancers, arrhythmia, and late-onset Alzheimer disease, these findings may trigger research directions and therapeutic development for these common diseases.

Published
2017
Full Text
View/download PDF

5. Expression of the neuropathy-associated MTMR2 gene rescues MTM1-associated myopathy

Author

Christine Kretz, Pascal Kessler, Belinda S. Cowling, Jocelyn Laporte, Sylvie Friant, Jean-Marie Xuereb, Bruno Rinaldi, Dimitri L. Bertazzi, Norma B. Romero, Matthieu A. Raess, Bernard Payrastre, Génétique moléculaire, génomique, microbiologie (GMGM), Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS), Institut de Génétique et de Biologie Moléculaire et Cellulaire (IGBMC), Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Institut des Maladies Métaboliques et Cardiovasculaires (I2MC), Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut de Myologie, Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Association française contre les myopathies (AFM-Téléthon)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM), and Centre National de la Recherche Scientifique (CNRS)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Association française contre les myopathies (AFM-Téléthon)-Sorbonne Université (SU)

Subjects
Male, 0301 basic medicine, Gene isoform, Biology, medicine.disease_cause, Mice, 03 medical and health sciences, 0302 clinical medicine, Protein Domains, Genetics, medicine, Animals, Humans, Protein Isoforms, Centronuclear myopathy, Myopathy, Molecular Biology, Genetics (clinical), Mice, Knockout, Mutation, [SDV.GEN]Life Sciences [q-bio]/Genetics, General Medicine, Protein Tyrosine Phosphatases, Non-Receptor, medicine.disease, Phenotype, Congenital myopathy, Cell biology, 030104 developmental biology, Knockout mouse, Heterologous expression, medicine.symptom, 030217 neurology & neurosurgery, Myopathies, Structural, Congenital
Abstract

Myotubularins (MTMs) are active or dead phosphoinositides phosphatases defining a large protein family conserved through evolution and implicated in different neuromuscular diseases. Loss-of-function mutations in MTM1 cause the severe congenital myopathy called myotubular myopathy (or X-linked centronuclear myopathy) while mutations in the MTM1-related protein MTMR2 cause a recessive Charcot-Marie-Tooth peripheral neuropathy. Here we aimed to determine the functional specificity and redundancy of MTM1 and MTMR2, and to assess their abilities to compensate for a potential therapeutic strategy. Using molecular investigations and heterologous expression of human MTMs in yeast cells and in Mtm1 knockout mice, we characterized several naturally occurring MTMR2 isoforms with different activities. We identified the N-terminal domain as responsible for functional differences between MTM1 and MTMR2. An N-terminal extension observed in MTMR2 is absent in MTM1, and only the short MTMR2 isoform lacking this N-terminal extension behaved similarly to MTM1 in yeast and mice. Moreover, adeno-associated virus-mediated exogenous expression of several MTMR2 isoforms ameliorates the myopathic phenotype owing to MTM1 loss, with increased muscle force, reduced myofiber atrophy, and reduction of the intracellular disorganization hallmarks associated with myotubular myopathy. Noteworthy, the short MTMR2 isoform provided a better rescue when compared with the long MTMR2 isoform. In conclusion, these results point to the molecular basis for MTMs functional specificity. They also provide the proof-of-concept that expression of the neuropathy-associated MTMR2 gene improves the MTM1-associated myopathy, thus identifying MTMR2 as a novel therapeutic target for myotubular myopathy.

Published
2017
Full Text
View/download PDF

6. Reducing dynamin 2 expression rescues X-linked centronuclear myopathy

Author

Ivana Prokic, Christine Kretz, Belinda S. Cowling, Thierry Chevremont, Arnaud Ferry, Norma B. Romero, Olga S. Koutsopoulos, Catherine Coirault, Jocelyn Laporte, Vincent Laugel, Institut de Génétique et de Biologie Moléculaire et Cellulaire (IGBMC), Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Thérapie des maladies du muscle strié, Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Institut de Myologie, Université Pierre et Marie Curie - Paris 6 (UPMC)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Association française contre les myopathies (AFM-Téléthon)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Université Paris Descartes - Paris 5 (UPD5), Hôpital de Hautepierre [Strasbourg], CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC), Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Institut de Génétique et de Biologie Moléculaire et Cellulaire ( IGBMC ), Université de Strasbourg ( UNISTRA ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ), Université Pierre et Marie Curie - Paris 6 ( UPMC ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ), Université Pierre et Marie Curie - Paris 6 ( UPMC ) -Commissariat à l'énergie atomique et aux énergies alternatives ( CEA ) -Assistance publique - Hôpitaux de Paris (AP-HP)-Association française contre les myopathies ( AFM-Téléthon ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ), Université Paris Descartes - Paris 5 ( UPD5 ), Unité de Morphologie Neuromusculaire, Université Pierre et Marie Curie - Paris 6 ( UPMC ) -Commissariat à l'énergie atomique et aux énergies alternatives ( CEA ) -Assistance publique - Hôpitaux de Paris (AP-HP)-Association française contre les myopathies ( AFM-Téléthon ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ) -Université Pierre et Marie Curie - Paris 6 ( UPMC ) -Commissariat à l'énergie atomique et aux énergies alternatives ( CEA ) -Assistance publique - Hôpitaux de Paris (AP-HP)-Association française contre les myopathies ( AFM-Téléthon ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ) -CHU Pitié-Salpêtrière [APHP], Centre de Référence de Pathologie Neuromusculaire Paris-Est, Centre for Integrative Biology - CBI (Inserm U964 - CNRS UMR7104 - IGBMC), Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Association française contre les myopathies (AFM-Téléthon)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Pierre et Marie Curie - Paris 6 (UPMC), Centre de recherche en myologie, Université Pierre et Marie Curie - Paris 6 (UPMC)-Association française contre les myopathies (AFM-Téléthon)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), CHU Strasbourg, Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Association française contre les myopathies (AFM-Téléthon)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Institut de génétique et biologie moléculaire et cellulaire (IGBMC), Université Louis Pasteur - Strasbourg I-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), HAL UPMC, Gestionnaire, and Centre National de la Recherche Scientifique (CNRS)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Association française contre les myopathies (AFM-Téléthon)-Sorbonne Université (SU)

Subjects
obesity, Myotubularin, [SDV]Life Sciences [q-bio], mechanical ventilation Trial Registration: Not applicable, [SDV.BC]Life Sciences [q-bio]/Cellular Biology, Biology, Dynamin II, 03 medical and health sciences, 0302 clinical medicine, Atrophy, [ SDV.MHEP ] Life Sciences [q-bio]/Human health and pathology, medicine, Sarcomere organization, 030304 developmental biology, Dynamin, Genetics, 0303 health sciences, [SDV.MHEP] Life Sciences [q-bio]/Human health and pathology, Skeletal muscle, Muscle weakness, General Medicine, medicine.disease, Cell biology, critical care, animal studies, DNM2, medicine.anatomical_structure, diaphragm, medicine.symptom, 030217 neurology & neurosurgery, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract

International audience; 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 in the gene encoding dynamin 2 (DNM2), and loss-of-function mutations in the gene encoding myotubularin (MTM1) result in X-linked CNM (XLCNM, also called myotubular myopathy), which promotes severe neonatal hypo-tonia and early death. Currently, no effective treatments exist for XLCNM. Here, we found increased DNM2 levels in XLCNM patients and a mouse model of XLCNM (Mtm1 –/y). Generation of Mtm1 –/y mice that were heterozygous for Dnm2 revealed that reduction of DNM2 in XLCNM mice restored life span, whole-body strength, and diaphragm function and increased muscle strength. Additionally, classic CNM-associated his-tological features, including fiber atrophy and nuclei mispositioning, were absent or reduced. Ultrastructur-al analysis revealed improvement of sarcomere organization and triad structures. Skeletal muscle–specific decrease of Dnm2 during embryogenesis or in young mice after disease onset revealed that the rescue associated with downregulation of Dnm2 is cell autonomous and is able to stop and potentially revert XLCNM progression. These data indicate that MTM1 and DNM2 regulate muscle organization and force through a common pathway. Furthermore, despite DNM2 being a key mechanoenzyme, its reduction is beneficial for XLCNM and represents a potential therapeutic approach for patients.

Published
2014
Full Text
View/download PDF

7. G.P.12.02 T-tubule disorganisation and defective excitation–contraction coupling in muscle fibres lacking myotubularin lipid phosphatase

Author

Nadia Messaddeq, Anna Buj-Bello, Céline Berbey, Christine Kretz, Vincent Jacquemond, Norbert Weiss, Despina Sanoudou, Jocelyn Laporte, Bruno Allard, Alan H. Beggs, L. Al-Qusairi, Jean-Louis Mandel, Approches génétiques intégrées et nouvelles thérapies pour les maladies rares (INTEGRARE), Université d'Évry-Val-d'Essonne (UEVE)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay-Généthon, and Généthon

Subjects
Myotubularin, Chemistry, Excitation–contraction coupling, Phosphatase, [SDV.BBM.BM]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Molecular biology, Cell biology, T-tubule, medicine.anatomical_structure, Neurology, Biochemistry, Pediatrics, Perinatology and Child Health, medicine, Neurology (clinical), Genetics (clinical), ComputingMilieux_MISCELLANEOUS
Abstract

International audience

Published
2009
Full Text
View/download PDF

8. Dementia in a child with myotubular myopathy

Author

Heather J. McCrea, Laura R. Ment, Christine Kretz, Jocelyn Laporte, Peney, Maité, Department of Cell Biology [New Haven], Yale School of Medicine [New Haven, Connecticut] (YSM)-Howard Hughes Medical Institute (HHMI), Institut de génétique et biologie moléculaire et cellulaire (IGBMC), Université Louis Pasteur - Strasbourg I-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Collège de France - Chaire Génétique Humaine, Collège de France (CdF (institution)), Department of Pediatrics, Yale School of Medicine [New Haven, Connecticut] (YSM), Department of Neurology, Yale University School of Medicine-Howard Hughes Medical Institute (HHMI), Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Louis Pasteur - Strasbourg I, Chaire Génétique Humaine, and Yale University School of Medicine

Subjects
Male, Pediatrics, medicine.medical_specialty, Pathology, MESH: Myopathies, Structural, Congenital, Article, MESH: Protein Tyrosine Phosphatases, Non-Receptor, Hypoxemia, Central nervous system disease, 03 medical and health sciences, 0302 clinical medicine, Degenerative disease, Developmental Neuroscience, Metabolic disturbance, MESH: Child, medicine, Humans, Dementia, Myotubular Myopathy, Child, 030304 developmental biology, Subclinical infection, 0303 health sciences, MESH: Humans, business.industry, Protein Tyrosine Phosphatases, Non-Receptor, medicine.disease, MESH: Dementia, MESH: Male, Neurology, El Niño, Pediatrics, Perinatology and Child Health, Neurology (clinical), medicine.symptom, business, 030217 neurology & neurosurgery, Myopathies, Structural, Congenital
Abstract

International audience; An 8-year old boy with genetically confirmed X-linked myotubular myopathy developed progressively worsening dementia and subclinical seizures at age 5-6 years. Previously, seizures or dementia have been noted in only a small number of myotubular myopathy patients, and only in association with significant metabolic disturbances. This patient had no evidence of hypoxemia or other metabolic disturbance. The present case suggests that the clinical spectrum of X-linked myotubular myopathy is broader than previously considered and may include mutation-dependent central nervous system disease.

Published
2009
Full Text
View/download PDF

9. C.P.1.10 Molecular mechanisms underlying X-linked myotubular myopathy

Author

Anna Buj-Bello, Christine Kretz, Jocelyn Laporte, Jean-Louis Mandel, Despina Sanoudou, L. Al-Qusairi, Alan H. Beggs, Approches génétiques intégrées et nouvelles thérapies pour les maladies rares (INTEGRARE), Université d'Évry-Val-d'Essonne (UEVE)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay-Généthon, and Généthon

Subjects
0303 health sciences, Chemistry, [SDV.BBM.BM]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Molecular biology, medicine.disease, X-linked myotubular myopathy, Molecular biology, 03 medical and health sciences, 0302 clinical medicine, Neurology, Pediatrics, Perinatology and Child Health, medicine, Neurology (clinical), 030217 neurology & neurosurgery, Genetics (clinical), ComputingMilieux_MISCELLANEOUS, 030304 developmental biology
Abstract

International audience

Published
2007
Full Text
View/download PDF

10. CXorf6 is a causative gene for hypospadias

Author

Christine Kretz, Agneta Nordenskjöld, Tsutomu Ogata, Gen Yamada, Kanako Miyabayashi, Ken Ichirou Morohashi, Giovanna Camerino, Ichizo Nishino, Yuka Wada, Anna Buj-Bello, Jocelyn Laporte, Tomonobu Hasegawa, Maki Fukami, Institut de génétique et biologie moléculaire et cellulaire (IGBMC), Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Louis Pasteur - Strasbourg I, and Université Louis Pasteur - Strasbourg I-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)

Subjects
Male, Sex Differentiation, Physiology, MESH: Base Sequence, Mice, 0302 clinical medicine, MESH: Pregnancy, Pregnancy, Testis, MESH: Gene Expression Regulation, Developmental, MESH: Animals, Disorders of sex development, MESH: Codon, Nonsense, In Situ Hybridization, 0303 health sciences, Hypospadias, MESH: Hypospadias, MESH: Testis, MESH: Infant, Newborn, MESH: Sex Differentiation, MESH: DNA, Causative gene, Gene Expression Regulation, Developmental, Pedigree, Codon, Nonsense, Female, medicine.medical_specialty, endocrine system, MESH: Pedigree, Period (gene), Nonsense mutation, 030209 endocrinology & metabolism, Biology, MESH: Chromosomes, Human, X, 03 medical and health sciences, Open Reading Frames, MESH: In Situ Hybridization, Internal medicine, Genetics, medicine, Animals, Humans, Gene, MESH: Mice, 030304 developmental biology, Fetus, Chromosomes, Human, X, MESH: Humans, Base Sequence, Infant, Newborn, [SDV.BBM.BM]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Molecular biology, DNA, MESH: Open Reading Frames, medicine.disease, MESH: Male, Endocrinology, MESH: Female
Abstract

International audience; 46,XY disorders of sex development (DSD) refer to a wide range of abnormal genitalia, including hypospadias, which affects approximately 0.5% of male newborns. We identified three different nonsense mutations of CXorf6 in individuals with hypospadias and found that its mouse homolog was specifically expressed in fetal Sertoli and Leydig cells around the critical period for sex development. These data imply that CXorf6 is a causative gene for hypospadias.

Published
2006
Full Text
View/download PDF

11. A novel PtdIns3P and PtdIns(3,5)P2 phosphatase with an inactivating variant in centronuclear myopathy

Author

Christine Kretz, Nicolas Dondaine, Jean-Louis Mandel, Bernard Payrastre, Valérie Tosch, Jocelyn Laporte, Nancy Monroy, Edmar Zanoteli, Holger Maria Rohde, Hélène Tronchère, Institut de génétique et biologie moléculaire et cellulaire (IGBMC), Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Louis Pasteur - Strasbourg I, Chaire Génétique Humaine, Collège de France (CdF (institution)), and Université Louis Pasteur - Strasbourg I-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)

Subjects
Male, Myotubularin, MESH: Catalytic Domain, Protein tyrosine phosphatase, MESH: Amino Acid Sequence, MESH: Variation (Genetics), MESH: Protein Structure, Tertiary, 0302 clinical medicine, Phosphatidylinositol Phosphates, Catalytic Domain, Chlorocebus aethiops, MESH: Animals, Genetics (clinical), Genetics, 0303 health sciences, MESH: Muscle, Skeletal, MESH: Protein-Tyrosine-Phosphatase, MESH: Arginine, General Medicine, Protein Tyrosine Phosphatases, Non-Receptor, MESH: Phosphatidylinositol Phosphates, Pedigree, Cell biology, MESH: COS Cells, COS Cells, MESH: Phosphoric Monoester Hydrolases, Female, Chromosomes, Human, Pair 3, medicine.symptom, Myopathies, Structural, Congenital, MESH: Myopathies, Structural, Congenital, MESH: Pedigree, Molecular Sequence Data, Phosphatase, MESH: Chromosomes, Human, Pair 3, Mutation, Missense, MESH: Sequence Alignment, Biology, Arginine, Transfection, Cell Line, 03 medical and health sciences, medicine, Animals, Humans, Amino Acid Sequence, Centronuclear myopathy, Muscle, Skeletal, Myopathy, Molecular Biology, 030304 developmental biology, Dynamin, MESH: Mutation, Missense, MESH: Humans, MESH: Molecular Sequence Data, MESH: Transfection, Genetic Variation, [SDV.BBM.BM]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Molecular biology, medicine.disease, Congenital myopathy, MESH: Cercopithecus aethiops, Phosphoric Monoester Hydrolases, MESH: Male, Protein Structure, Tertiary, MESH: Cell Line, DNM2, Protein Tyrosine Phosphatases, Sequence Alignment, MESH: Female, 030217 neurology & neurosurgery
Abstract

International audience; In eukaryotic cells, phosphoinositides are lipid second messengers important for many cellular processes and have been found dysregulated in several human diseases. X-linked myotubular (centronuclear) myopathy is a severe congenital myopathy caused by mutations in a phosphatidylinositol 3-phosphate (PtdIns3P) phosphatase called myotubularin, and mutations in dominant centronuclear myopathy (CNM) cases were identified in the dynamin 2 gene. The genes mutated in autosomal recessive cases of CNMs have not been found. We have identified a novel phosphoinositide phosphatase (hJUMPY) conserved through evolution, which dephosphorylates the same substrates as myotubularin, PtdIns3P and PtdIns(3,5)P(2), in vitro and ex vivo. We found, in sporadic cases of CNMs, two missense variants that affect the enzymatic function. One of these appeared de novo in a patient also carrying a de novo mutation in the dynamin 2 gene. The other missense (R336Q) found in another patient changes the catalytic arginine residue of the core phosphatase signature present in protein tyrosine/dual-specificity phosphatases and in phosphoinositide phosphatases and drastically reduces the enzymatic activity both in vitro and in transfected cells. The inheritance of the phenotype with regard to this variant is still unclear and could be either recessive with an undetected second allele or digenic. We propose that impairment of hJUMPY function is implicated in some cases of autosomal CNM and that hJUMPY cooperates with myotubularin to regulate the level of phosphoinositides in skeletal muscle.

Published
2006
Full Text
View/download PDF

12. Deletion of both MTM1 and MTMR1 genes in a boy with myotubular myopathy

Author

Jean-Louis Mandel, Christine Kretz, Anna Buj-Bello, Alberto Alain Gabbai, Acary Souza Bulle Oliveira, José Claudio Casali da Rocha, Edmar Zanoteli, Jocelyn Laporte, Ana Beatriz Alvarez Perez, Institut de génétique et biologie moléculaire et cellulaire (IGBMC), Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Louis Pasteur - Strasbourg I, Chaire Génétique Humaine, Collège de France (CdF (institution)), Approches génétiques intégrées et nouvelles thérapies pour les maladies rares (INTEGRARE), Université d'Évry-Val-d'Essonne (UEVE)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay-Généthon, Généthon, and Université Louis Pasteur - Strasbourg I-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)

Subjects
Genetics, 0303 health sciences, MESH: Humans, MESH: Protein-Tyrosine-Phosphatase, MESH: Myopathies, Structural, Congenital, MESH: Child, Preschool, [SDV.BBM.BM]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Molecular biology, Protein tyrosine phosphatase, Biology, Gene deletion, MESH: Male, 03 medical and health sciences, Exon, 0302 clinical medicine, MESH: Gene Deletion, MESH: Blotting, Southern, Myotubular Myopathy, MESH: Exons, Gene, 030217 neurology & neurosurgery, Genetics (clinical), ComputingMilieux_MISCELLANEOUS, 030304 developmental biology
Abstract

International audience

Published
2005
Full Text
View/download PDF

Catalog

Books, media, physical & digital resources
See catalog results