論文

査読有り
2013年

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.

Experimental animals
  • Nami Masubuchi
  • ,
  • Yuichi Shidoh
  • ,
  • Shunzo Kondo
  • ,
  • Jun Takatoh
  • ,
  • Kazunori Hanaoka

62
3
開始ページ
211
終了ページ
7
記述言語
英語
掲載種別
研究論文(学術雑誌)

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.

リンク情報
PubMed
https://www.ncbi.nlm.nih.gov/pubmed/23903056
PubMed Central
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4160940

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