Dystrophin Dp116: A yet to Be Investigated Product of the Duchenne Muscular Dystrophy Gene

Matsuo, Masafumi; Awano, Hiroyuki; Matsumoto, Masaaki; Nagai, Masashi; Kawaguchi, Tatsuya; Zhang, Zhujun; Nishio, Hisahide

doi:10.3390/genes8100251

Cited by 15 publications

(12 citation statements)

References 57 publications

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“…Dp116 is a Schwann cell‐specific isoform encoded by Dmd exons 56–79 [19]. We confirmed the presence of Dp116 expression in Dmd EGFP‐mdx mice following co‐immunostaining of a peripheral motor nerve branch and in a transverse section of the sciatic nerve using an anti‐GFP antibody for signal enhancement along with β‐tubulin III as neuronal marker (Figure S2A, B, Videos S1 and S2).…”

Section: Resultssupporting

confidence: 71%

Live‐imaging of revertant and therapeutically restored dystrophin in the Dmd^EGFP‐mdx mouse model for Duchenne muscular dystrophy

Petkova

Stantzou

Morin

et al. 2020

Neuropathology Appl Neurobio

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Neuropathology and Applied Neurobiology 46, 602-614 Live-imaging of revertant and therapeutically restored dystrophin in the Dmd EGFP-mdx mouse model for Duchenne muscular dystrophy Background: Dmd mdx , harbouring the c.2983C>T nonsense mutation in Dmd exon 23, is a mouse model for Duchenne muscular dystrophy (DMD), frequently used to test therapies aimed at dystrophin restoration. Current translational research is methodologically hampered by the lack of a reporter mouse model, which would allow direct visualization of dystrophin expression as well as longitudinal in vivo studies. Methods: We generated a Dmd EGFP-mdx reporter allele carrying in cis the mdx-23 mutation and a C-terminal EGFPtag. This mouse model allows direct visualization of spontaneously and therapeutically restored dystrophin-EGFP fusion protein either after natural fibre reversion, or for example, after splice modulation using tricyclo-DNA to skip Dmd exon 23, or after gene editing using AAV-encoded CRISPR/Cas9 for Dmd exon 23 excision. Results: Intravital microscopy in anaesthetized mice allowed live-imaging of sarcolemmal dystrophin-EGFP fusion protein of revertant fibres as well as following therapeutic restoration. Dystrophin-EGFPfluorescence persisted ex vivo, allowing live-imaging of revertant and therapeutically restored dystrophin in isolated fibres ex vivo. Expression of the shorter dystrophin-EGFP isoforms Dp71 in the brain, Dp260 in the retina, and Dp116 in the peripheral nerve remained unabated by the mdx-23 mutation. Conclusion: Intravital imaging of Dmd EGFP-mdx muscle permits novel experimental approaches such as the study of revertant and therapeutically restored dystrophin in vivo and ex vivo.

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Section: Resultssupporting

confidence: 71%

Live‐imaging of revertant and therapeutically restored dystrophin in the Dmd^EGFP‐mdx mouse model for Duchenne muscular dystrophy

Petkova

Stantzou

Morin

et al. 2020

Neuropathology Appl Neurobio

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“…Next to multiple splice variants of Dp140, an isoform with a size of 116 kDa is known to exist. 31 Moreover, a protein band appeared about the size of 40 kDa. Even though an isoform is known with a protein size of 40 kDa, we would not be able to detect this because the C-terminal that the antibody used is missing in this variant.…”

Section: Discussionmentioning

confidence: 99%

Dystrophin is expressed in smooth muscle and afferent nerve fibers in the rat urinary bladder

et al. 2019

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Introduction With increasing life expectancy, comorbidities become overt in Duchenne muscular dystrophy (DMD). Although micturition problems are common, bladder function is poorly understood in DMD. We studied dystrophin expression and multiple isoform involvement in the bladder during maturation to gain insights into their roles in micturition. Methods Dystrophin distribution was evaluated in rat bladders by immunohistochemical colocalization with smooth muscle, interstitial, urothelial, and neuronal markers. Protein levels of Dp140, Dp71, and smooth muscle were quantitated by Western blotting of neonatal to adult rat bladders. Results Dystrophin colocalized with smooth muscle cells and afferent nerve fibers. Dp71 was expressed two‐ to threefold higher compared with Dp140, independently of age. Age‐related muscle mass changes did not influence isoform expression levels. Discussion Dystrophin is expressed in smooth muscle cells and afferent nerve fibers in the urinary bladder, which underscores that micturition problems in DMD may have not solely a myogenic but also a neurogenic origin. Muscle Nerve 60: 202–210, 2019

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“…Dp140 is expressed in the brain, retina, and kidneys where it appears to be involved in brain development and blood flow regulation [ 45 , 46 , 47 ]. Dp116 is produced in Schwann cells, however, its role in this context is poorly understood [ 48 ]. Dp71 is ubiquitously expressed, it is found in most non-muscle tissues such as brain, kidney, liver, retina, and lung.…”

Section: Dystrophin—from Gene To Proteinmentioning

confidence: 99%

Dystrophin Cardiomyopathies: Clinical Management, Molecular Pathogenesis and Evolution towards Precision Medicine

D’Amario

Gowran

Canonico

et al. 2018

JCM

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Duchenne’s muscular dystrophy is an X-linked neuromuscular disease that manifests as muscle atrophy and cardiomyopathy in young boys. However, a considerable percentage of carrier females are often diagnosed with cardiomyopathy at an advanced stage. Existing therapy is not disease-specific and has limited effect, thus many patients and symptomatic carrier females prematurely die due to heart failure. Early detection is one of the major challenges that muscular dystrophy patients, carrier females, family members and, research and medical teams face in the complex course of dystrophic cardiomyopathy management. Despite the widespread adoption of advanced imaging modalities such as cardiac magnetic resonance, there is much scope for refining the diagnosis and treatment of dystrophic cardiomyopathy. This comprehensive review will focus on the pertinent clinical aspects of cardiac disease in muscular dystrophy while also providing a detailed consideration of the known and developing concepts in the pathophysiology of muscular dystrophy and forthcoming therapeutic options.

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Dystrophin Dp116: A yet to Be Investigated Product of the Duchenne Muscular Dystrophy Gene

Cited by 15 publications

References 57 publications

Live‐imaging of revertant and therapeutically restored dystrophin in the Dmd^EGFP‐mdx mouse model for Duchenne muscular dystrophy

Live‐imaging of revertant and therapeutically restored dystrophin in the Dmd^EGFP‐mdx mouse model for Duchenne muscular dystrophy

Dystrophin is expressed in smooth muscle and afferent nerve fibers in the rat urinary bladder

Dystrophin Cardiomyopathies: Clinical Management, Molecular Pathogenesis and Evolution towards Precision Medicine

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Dystrophin Dp116: A yet to Be Investigated Product of the Duchenne Muscular Dystrophy Gene

Cited by 15 publications

References 57 publications

Live‐imaging of revertant and therapeutically restored dystrophin in the DmdEGFP‐mdx mouse model for Duchenne muscular dystrophy

Live‐imaging of revertant and therapeutically restored dystrophin in the DmdEGFP‐mdx mouse model for Duchenne muscular dystrophy

Dystrophin is expressed in smooth muscle and afferent nerve fibers in the rat urinary bladder

Dystrophin Cardiomyopathies: Clinical Management, Molecular Pathogenesis and Evolution towards Precision Medicine

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Live‐imaging of revertant and therapeutically restored dystrophin in the Dmd^EGFP‐mdx mouse model for Duchenne muscular dystrophy

Live‐imaging of revertant and therapeutically restored dystrophin in the Dmd^EGFP‐mdx mouse model for Duchenne muscular dystrophy