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

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          ABSTRACT

          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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          Most cited references33

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          The Dystrophin Complex: Structure, Function, and Implications for Therapy.

          The dystrophin complex stabilizes the plasma membrane of striated muscle cells. Loss of function mutations in the genes encoding dystrophin, or the associated proteins, trigger instability of the plasma membrane, and myofiber loss. Mutations in dystrophin have been extensively cataloged, providing remarkable structure-function correlation between predicted protein structure and clinical outcomes. These data have highlighted dystrophin regions necessary for in vivo function and fueled the design of viral vectors and now, exon skipping approaches for use in dystrophin restoration therapies. However, dystrophin restoration is likely more complex, owing to the role of the dystrophin complex as a broad cytoskeletal integrator. This review will focus on dystrophin restoration, with emphasis on the regions of dystrophin essential for interacting with its associated proteins and discuss the structural implications of these approaches.
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            Duchenne muscular dystrophy.

            Duchenne muscular dystrophy, an X-linked disorder, has an incidence of one in 5000 boys and presents in early childhood with proximal muscle weakness. Untreated boys become wheelchair bound by the age of 12 years and die of cardiorespiratory complications in their late teens to early 20s. The use of corticosteroids, non-invasive respiratory support, and active surveillance and management of associated complications have improved ambulation, function, quality of life and life expectancy. The clinical features, investigations and management of Duchenne muscular dystrophy are reviewed, as well as the latest in some of the novel therapies.
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              Dystrophin-deficient cardiomyocytes are abnormally vulnerable to mechanical stress-induced contractile failure and injury.

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                Author and article information

                Contributors
                judith.lionarons@mumc.nl
                Journal
                Muscle Nerve
                Muscle Nerve
                10.1002/(ISSN)1097-4598
                MUS
                Muscle & Nerve
                John Wiley & Sons, Inc. (Hoboken, USA )
                0148-639X
                1097-4598
                07 June 2019
                August 2019
                : 60
                : 2 ( doiID: 10.1002/mus.v60.2 )
                : 202-210
                Affiliations
                [ 1 ] Department of Neurology Maastricht University Medical Center PO Box 5800, 6202 AZ Maastricht The Netherlands
                [ 2 ] School for Mental Health & Neuroscience Maastricht University Maastricht The Netherlands
                [ 3 ] Department of Neurosurgery Maastricht University Medical Center Maastricht The Netherlands
                [ 4 ] Department of Urology Maastricht University Medical Center Maastricht The Netherlands
                Author notes
                [*] [* ] Correspondence to: J. M. Lionarons; e‐mail: judith.lionarons@ 123456mumc.nl
                Article
                MUS26518
                10.1002/mus.26518
                6771971
                31095755
                066cb5ea-b779-4de4-80d3-fbc42ab605e3
                © 2019 The Authors. Muscle & Nerve published by Wiley Periodicals, Inc.

                This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.

                History
                : 28 September 2018
                : 08 May 2019
                : 11 May 2019
                Page count
                Figures: 4, Tables: 0, Pages: 9, Words: 6804
                Categories
                Basic Science Research Article
                Basic Science Research Articles
                Custom metadata
                2.0
                mus26518
                August 2019
                Converter:WILEY_ML3GV2_TO_NLMPMC version:5.6.9 mode:remove_FC converted:01.10.2019

                Neurosciences
                duchenne muscular dystrophy,dystrophin,human urinary bladder,lower urinary tract symptoms,maturation,micturition,rat urinary bladder

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