Transgenic mdx mice expressing dystrophin with a deletion in the actin- binding domain display a 'mild Becker' phenotype

Kathleen Corrado, Jill A. Rafael, Patti L. Mills, Neil M. Cole, John A. Faulkner, Kuan Wang, Jeffrey S. Chamberlain

研究成果: 雜誌貢獻文章同行評審

74 引文 斯高帕斯(Scopus)

摘要

The functional significance of the actin-binding domain of dystrophin, the protein lacking in patients with Duchenne muscular dystrophy, has remained elusive. Patients with deletions of this domain (domain I) typically express low levels of the truncated protein. Whether the moderate to severe phenotypes associated with such deletions result from loss of an essential function, or from reduced levels of a functional protein, is unclear. To address this question, we have generated transgenic mice that express wild- type levels of a dystrophin deleted for the majority of the actin-binding domain. The transgene derived protein lacks amino acids 45-273, removing 2 of 3 in vitro identified actin interacting sites and part of hinge 1. Examination of the effect of this deletion in mice lacking wild-type dystrophin (mdx) suggests that a functional domain I is not essential for prevention of a dystrophic phenotype. However, in contrast to deletions in the central rod domain and to full-length dystrophin, both of which are functional at only 20% of wild-type levels, proteins with a deletion in domain I must be expressed at high levels to prevent a severe dystrophy. These results are also in contrast to the severe dystrophy resulting from truncation of the COOH-terminal domain that links dystrophin to the extracellular matrix. The mild phenotype observed in mice with domain I- deletions indicates that an intact actin-binding domain is not essential, although it does contribute to an important function of dystrophin. These studies also suggest the link between dystrophin and the subsarcolemmal cytoskeleton involves more than a simple attachment of domain I to actin filaments.

原文英語
頁(從 - 到)873-884
頁數12
期刊Journal of Cell Biology
134
發行號4
DOIs
出版狀態已發佈 - 8月 1996
對外發佈

ASJC Scopus subject areas

  • 細胞生物學

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