Format

Send to

Choose Destination
Mol Biol Cell. 2009 Jan;20(1):146-52. doi: 10.1091/mbc.E08-08-0811. Epub 2008 Oct 22.

Amelioration of muscular dystrophy by transgenic expression of Niemann-Pick C1.

Author information

1
Department of Physiology and Biophysics, University of Washington, Seattle, WA 98195, USA.

Abstract

Duchenne muscular dystrophy (DMD) and other types of muscular dystrophies are caused by the loss or alteration of different members of the dystrophin protein complex. Understanding the molecular mechanisms by which dystrophin-associated protein abnormalities contribute to the onset of muscular dystrophy may identify new therapeutic approaches to these human disorders. By examining gene expression alterations in mouse skeletal muscle lacking alpha-dystrobrevin (Dtna(-/-)), we identified a highly significant reduction of the cholesterol trafficking protein, Niemann-Pick C1 (NPC1). Mutations in NPC1 cause a progressive neurodegenerative, lysosomal storage disorder. Transgenic expression of NPC1 in skeletal muscle ameliorates muscular dystrophy in the Dtna(-/-) mouse (which has a relatively mild dystrophic phenotype) and in the mdx mouse, a model for DMD. These results identify a new compensatory gene for muscular dystrophy and reveal a potential new therapeutic target for DMD.

PMID:
18946078
PMCID:
PMC2613093
DOI:
10.1091/mbc.e08-08-0811
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for Atypon Icon for PubMed Central
Loading ...
Support Center