Document Detail

Skeletal muscle gene expression after myostatin knockout in mature mice.
MedLine Citation:
PMID:  19509079     Owner:  NLM     Status:  MEDLINE    
There is much interest in developing anti-myostatin agents to reverse or prevent muscle atrophy in adults, so it is important to characterize the effects of reducing myostatin activity after normal muscle development. For assessment of the effect of loss of myostatin signaling on gene expression in muscle, RNA from mice with postdevelopmental myostatin knockout was analyzed with oligonucleotide microarrays. Myostatin was undetectable in muscle within 2 wk after Cre recombinase activation in 4-month-old male mice with floxed myostatin genes. Three months after myostatin depletion, muscle mass had increased 26% (vs. 2% after induction of Cre activity in mice with normal myostatin genes), at which time the expression of several hundred genes differed in knockout and control mice at nominal P < 0.01. In contrast to previously reported effects of constitutive myostatin knockout, postdevelopmental knockout did not downregulate expression of genes encoding slow isoforms of contractile proteins or genes encoding proteins involved in energy metabolism. Several collagen genes were expressed at 20-50% lower levels in the myostatin-deficient muscles, which had approximately 25% less collagen than normal muscles as reflected by hydroxyproline content. Most of the other genes affected by myostatin depletion have not been previously linked to myostatin signaling. Gene set enrichment analysis suggested that Smads are not the only transcription factors with reduced activity after myostatin depletion. These data reinforce other evidence that myostatin regulates collagen production in muscle and demonstrate that many of the previously reported effects of constitutive myostatin deficiency do not occur when myostatin is knocked out in mature muscles.
Stephen Welle; Andrew Cardillo; Michelle Zanche; Rabi Tawil
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural     Date:  2009-06-09
Journal Detail:
Title:  Physiological genomics     Volume:  38     ISSN:  1531-2267     ISO Abbreviation:  Physiol. Genomics     Publication Date:  2009 Aug 
Date Detail:
Created Date:  2009-08-11     Completed Date:  2010-01-13     Revised Date:  2013-09-18    
Medline Journal Info:
Nlm Unique ID:  9815683     Medline TA:  Physiol Genomics     Country:  United States    
Other Details:
Languages:  eng     Pagination:  342-50     Citation Subset:  IM    
Department of Medicine, University of Rochester, Rochester, New York, USA.
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MeSH Terms
Blotting, Western
Collagen / genetics
Energy Metabolism / genetics
Gene Expression Profiling*
Gene Expression Regulation
Gene Knockdown Techniques / methods*
Mitochondrial Proteins / genetics
Muscle, Skeletal / metabolism*
Myostatin / genetics,  metabolism,  physiology*
Oligonucleotide Array Sequence Analysis
Reverse Transcriptase Polymerase Chain Reaction
Grant Support
Reg. No./Substance:
0/Mitochondrial Proteins; 0/Myostatin; 9007-34-5/Collagen

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

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