title: Subcellular localization of dystrophin isoforms in cardiomyocytes and phenotypic analysis of dystrophin-deficient mice reveal cardiac myopathy is predominantly caused by a deficiency in full-length dystrophin.
abstract: Duchenne muscular dystrophy (DMD) is an X-linked recessive progressive muscle degenerative disorder that causes dilated cardiomyopathy in the second decade of life in affected males. Dystrophin, the gene responsible for DMD, encodes full-length dystrophin and various short dystrophin isoforms. In the mouse heart, full-length dystrophin Dp427 and a short dystrophin isoform, Dp71, are expressed. In this study, we intended to clarify the functions of these dystrophin isoforms in DMD-related cardiomyopathy. We used two strains of mice: mdx mice, in which Dp427 was absent but Dp71 was present, and DMD-null mice, in which both were absent. By immunohistochemical staining and density-gradient centrifugation, we found that Dp427 was located in the cardiac sarcolemma and also at the T-tubules, whereas Dp71 was specifically located at the T-tubules. In order to determine whether T tubule-associated Dp71 was involved in DMD-related cardiac disruption, we compared the cardiac phenotypes between DMD-null mice and mdx mice. Both DMD-null mice and mdx mice exhibited severe necrosis, which was followed by fibrosis in cardiac muscle. However, we could not detect a significant difference in myocardial fibrosis between mdx mice and DMD-null mice. Based on the present results, we have shown that cardiac myopathy is caused predominantly by a deficiency of full-length dystrophin Dp427.
authors.affiliation: Laboratory of Molecular Embryology, Department of Bioscience, Kitasato University School of Science, 1-15-1 Kitasato, Minami-Ku, Sagamihara, Kanagawa 252-0373, Japan.
authors.forename: Nami
authors.initials: N
authors.lastname: Masubuchi
authors.forename: Yuichi
authors.initials: Y
authors.lastname: Shidoh
authors.forename: Shunzo
authors.initials: S
authors.lastname: Kondo
authors.forename: Jun
authors.initials: J
authors.lastname: Takatoh
authors.forename: Kazunori
authors.initials: K
authors.lastname: Hanaoka
mesh_terms: D000818:Animals; D009202:Cardiomyopathies / Q000235:genetics*; D016189:Dystrophin / Q000172:deficiency* / Q000235:genetics*; D005355:Fibrosis; D051379:Mice; D008810:Mice, Inbred C57BL; D008808:Mice, Inbred CBA; D008815:Mice, Inbred Strains; D009206:Myocardium / Q000166:cytology / Q000473:pathology; D032383:Myocytes, Cardiac / Q000166:cytology / Q000378:metabolism* / Q000473:pathology; D010641:Phenotype; D020033:Protein Isoforms / Q000235:genetics; D012508:Sarcolemma / Q000378:metabolism
chemical_list: D016189:Dystrophin; D020033:Protein Isoforms
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