Dystrophin deficiency in canine X-linked muscular dystrophy in Japan CXMDJ alters myosin heavy chain expression profiles in the diaphragm more markedly than in the tibialis cranialis muscleReportar como inadecuado




Dystrophin deficiency in canine X-linked muscular dystrophy in Japan CXMDJ alters myosin heavy chain expression profiles in the diaphragm more markedly than in the tibialis cranialis muscle - Descarga este documento en PDF. Documentación en PDF para descargar gratis. Disponible también para leer online.

BMC Musculoskeletal Disorders

, 9:1

First Online: 09 January 2008Received: 28 September 2007Accepted: 09 January 2008

Abstract

BackgroundSkeletal muscles are composed of heterogeneous collections of muscle fiber types, the arrangement of which contributes to a variety of functional capabilities in many muscle types. Furthermore, skeletal muscles can adapt individual myofibers under various circumstances, such as disease and exercise, by changing fiber types. This study was performed to examine the influence of dystrophin deficiency on fiber type composition of skeletal muscles in canine X-linked muscular dystrophy in Japan CXMDJ, a large animal model for Duchenne muscular dystrophy.

MethodsWe used tibialis cranialis TC muscles and diaphragms of normal dogs and those with CXMDJ at various ages from 1 month to 3 years old. For classification of fiber types, muscle sections were immunostained with antibodies against fast, slow, or developmental myosin heavy chain MHC, and the number and size of these fibers were analyzed. In addition, MHC isoforms were detected by gel electrophoresis.

ResultsIn comparison with TC muscles of CXMDJ, the number of fibers expressing slow MHC increased markedly and the number of fibers expressing fast MHC decreased with growth in the affected diaphragm. In populations of muscle fibers expressing fast and-or slow MHCs but not developmental MHC of CXMDJ muscles, slow MHC fibers were predominant in number and showed selective enlargement. Especially, in CXMDJ diaphragms, the proportions of slow MHC fibers were significantly larger in populations of myofibers with non-expression of developmental MHC. Analyses of MHC isoforms also indicated a marked increase of type I and decrease of type IIA isoforms in the affected diaphragm at ages over 6 months. In addition, expression of developmental embryonic and-or neonatal MHC decreased in the CXMDJ diaphragm in adults, in contrast to continuous high-level expression in affected TC muscle.

ConclusionThe CXMDJ diaphragm showed marked changes in fiber type composition unlike TC muscles, suggesting that the affected diaphragm may be effectively adapted toward dystrophic stress by switching to predominantly slow fibers. Furthermore, the MHC expression profile in the CXMDJ diaphragm was markedly different from that in mdx mice, indicating that the dystrophic dog is a more appropriate model than a murine one, to investigate the mechanisms of respiratory failure in DMD.

Electronic supplementary materialThe online version of this article doi:10.1186-1471-2474-9-1 contains supplementary material, which is available to authorized users.

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Autor: Katsutoshi Yuasa - Akinori Nakamura - Takao Hijikata - Shinichi Takeda

Fuente: https://link.springer.com/







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