Developmental Alterations in Heart Biomechanics and Skeletal Muscle Function in Desmin Mutants Suggest an Early Pathological Root for Desminopathies

Ramspacher, Caroline; Steed, Emily; Boselli, Francesco; Ferreira, Rita R.; Faggianelli, Nathalie; Roth, Stéphane; Spiegelhalter, Coralie; Messaddeq, Nadia; Trinh, Le A.; Liebling, Michael; Chacko, Nikhil; Tessadori, Federico; Bakkers, Jeroen; Laporte, Jocelyn; Hnia, Karim; Vermot, Julien

doi:10.1016/j.celrep.2015.05.010

Cited by 42 publications

(33 citation statements)

References 47 publications

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“…In particular, the affected flies display locomotor defects associated with alterations of muscle structure and ultrastructure. Recently, transgenic zebrafish have been generated by inserting fluorescent labels (citrine or mCherry) into the zebrafish desmin “a” gene [35]. The expression of the modified genes leads to desmin aggregation in skeletal and cardiac muscles, 48 h after the beginning of embryonic development.…”

Section: Mfm Animal Modelsmentioning

confidence: 99%

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Myofibrillar Myopathies: New Perspectives from Animal Models to Potential Therapeutic Approaches

Batonnet-Pichon

Béhin

Cabet

et al. 2017

JND

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Myofibrillar myopathies (MFMs) are muscular disorders involving proteins that play a role in the structure, maintenance processes and protein quality control mechanisms closely related to the Z-disc in the muscular fibers. MFMs share common histological characteristics including progressive disorganization of the interfibrillar network and protein aggregation. Currently no treatment is available. In this review, we describe first clinical symptoms associated with mutations of the six genes (DES, CRYAB, MYOT, ZASP, FLNC and BAG3) primary involved in MFM and defining the origin of this pathology. As mechanisms determining the aetiology of the disease remain unclear yet, several research teams have developed animal models from invertebrates to mammalians species. Thus we describe here these different models that often recapitulate human clinical symptoms. Therefore they are very useful for deeper studies to understand early molecular and progressive mechanisms determining the pathology. Finally in the last part, we emphasize on the potential therapeutic approaches for MFM that could be conducted in the future. In conclusion, this review offers a link from patients to future therapy through the use of MFMs animal models.

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Section: Mfm Animal Modelsmentioning

confidence: 99%

“…These defects are associated with perturbations of excitation-contraction coupling mechanisms involving calcium, sarcoplasmic reticulum and abnormal distribution of ryanodine receptors. Interestingly, desmin knockdown or pharmacological inhibition of desmin aggregates reverted these phenotypes [35]. …”

Section: Mfm Animal Modelsmentioning

confidence: 99%

Myofibrillar Myopathies: New Perspectives from Animal Models to Potential Therapeutic Approaches

Batonnet-Pichon

Béhin

Cabet

et al. 2017

JND

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“…Mutations in this domain may lead to severe disruption of the desmin filament assembly process (Fig. 1d) [11,12]. At present, approximately 10 mutations have been identified in DCM patients [8].…”

Section: Discussionmentioning

confidence: 99%

Exome Sequencing Identifies a Novel <b><i>DES</i></b> Mutation (R227C) in a Chinese Dilated Cardiomyopathy Family

Liu²,

Chen³

2017

Cardiology

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Objectives: Dilated cardiomyopathy (DCM) is a common disease in the clinic, and it is the leading cause of heart failure and sudden cardiac death. Previous studies have proven that genetic factors play a crucial role in the occurrence of DCM; more than 50 disease genes including desmin (DES) have been identified to be associated with DCM. At present, most DES mutations are reported in desmin-related myofibrilla myopathy patients, but variants leading to isolated DCM are rarely reported. Methods: We applied whole-exome sequencing and cardiomyopathy-related gene filtering strategies to discover the genetic factors in a Chinese DCM family. Results: A novel mutation (c.679 C>T /p.R227C) in exon 3 of DES was identified and cosegregated with the affected members of a Chinese family with isolated DCM phenotypes (left ventricle and left atrial diameters). Conclusion: This mutation leads to a substitution of arginine by cysteine and it is predicted to be deleterious by bioinformatics programs. Our study not only contributes to the genetic diagnosis and counseling of families with DCM, but it also further proves that DES mutations may lead to isolated DCM and provides a new case for the study of the relationship between DES mutations and DCM.

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“…SHG allows to visualize endogenous, non-centrosymmetric molecules, such as collagen and myosin, which upon light scattering produce a photon at half the incident wavelength. SHG has been proven to be a highly useful technology for the non-invasive intravital imaging of the collagenrich microenvironment during tumor invasion (Wang et al, 2002), of muscle defects in the mouse ear and of zebrafish embryos (Ramspacher et al, 2015). Furthermore, nanoparticles generating second harmonics have been used in vivo and represent new imaging tools (Grange et al, 2011;Pantazis et al, 2010).…”

Section: Label-free Intravital Imagingmentioning

confidence: 99%

Seeing is believing: multi-scale spatio-temporal imaging towards in vivo cell biology

Follain

Mercier

Osmani

et al. 2016

Journal of Cell Science

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Life is driven by a set of biological events that are naturally dynamic and tightly orchestrated from the single molecule to entire organisms. Although biochemistry and molecular biology have been essential in deciphering signaling at a cellular and organismal level, biological imaging has been instrumental for unraveling life processes across multiple scales. Imaging methods have considerably improved over the past decades and now allow to grasp the inner workings of proteins, organelles, cells, organs and whole organisms. Not only do they allow us to visualize these events in their most-relevant context but also to accurately quantify underlying biomechanical features and, so, provide essential information for their understanding. In this Commentary, we review a palette of imaging (and biophysical) methods that are available to the scientific community for elucidating a wide array of biological events. We cover the most-recent developments in intravital imaging, light-sheet microscopy, superresolution imaging, and correlative light and electron microscopy. In addition, we illustrate how these technologies have led to important insights in cell biology, from the molecular to the whole-organism resolution. Altogether, this review offers a snapshot of the current and state-of-the-art imaging methods that will contribute to the understanding of life and disease.

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Developmental Alterations in Heart Biomechanics and Skeletal Muscle Function in Desmin Mutants Suggest an Early Pathological Root for Desminopathies

Cited by 42 publications

References 47 publications

Myofibrillar Myopathies: New Perspectives from Animal Models to Potential Therapeutic Approaches

Myofibrillar Myopathies: New Perspectives from Animal Models to Potential Therapeutic Approaches

Exome Sequencing Identifies a Novel <b><i>DES</i></b> Mutation (R227C) in a Chinese Dilated Cardiomyopathy Family

Seeing is believing: multi-scale spatio-temporal imaging towards in vivo cell biology

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