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GENES & DEVELOPMENT 21:770-783, 2007
©2007 by Cold Spring Harbor Laboratory Press; ISSN 0890-9369/ $5.00
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PGC-1{alpha} regulates the neuromuscular junction program and ameliorates Duchenne muscular dystrophy

Christoph Handschin1,2, Yvonne M. Kobayashi3, Sherry Chin1, Patrick Seale1, Kevin P. Campbell3, and Bruce M. Spiegelman1,4

1 Dana-Farber Cancer Institute and Department of Cell Biology, Harvard Medical School, Boston, Massachusetts 02115, USA; 2 Institute of Physiology and Zurich Center for Integrative Human Physiology, University of Zurich, CH-8057 Zurich, Switzerland; 3 Howard Hughes Medical Institute and Departments of Molecular Physiology and Biophysics, Neurology, and Internal Medicine, University of Iowa, Roy J. and Lucille A. Carver College of Medicine, Iowa City, Iowa 52242, USA

The coactivator PGC-1{alpha} mediates key responses of skeletal muscle to motor nerve activity. We show here that neuregulin-stimulated phosphorylation of PGC-1{alpha} and GA-binding protein (GABP) allows recruitment of PGC-1{alpha} to the GABP complex and enhances transcription of a broad neuromuscular junction gene program. Since a subset of genes controlled by PGC-1{alpha} and GABP is dysregulated in Duchenne muscular dystrophy (DMD), we examined the effects of transgenic PGC-1{alpha} in muscle of mdx mice. These animals show improvement in parameters characteristic of DMD, including muscle histology, running performance, and plasma creatine kinase levels. Thus, control of PGC-1{alpha} levels in skeletal muscle could represent a novel avenue to prevent or treat DMD.

[Keywords: PGC-1; neuromuscular junction; GA-binding protein; Duchenne muscular dystrophy; transcriptional regulation]

Received December 21, 2006; revised version accepted February 8, 2007.

4 Corresponding author.

E-MAIL bruce_spiegelman{at}dfci.harvard.edu; FAX (617) 632-4655.

Supplemental material is available at http://www.genesdev.org.

Article is online at http://www.genesdev.org/cgi/doi/10.1101/gad.1525107


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