Physiol. Genomics Journal of Applied Physiology
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Physiol. Genomics (October 12, 2004). doi:10.1152/physiolgenomics.00100.2004
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Submitted on April 23, 2004
Accepted on October 11, 2004

Transcriptional Reprogramming and Ultrastructure during Atrophy and Recovery of Mouse Soleus Muscle

Christoph Dapp1*, Silvia Schmutz1, Hans Hoppeler1, and Martin Fluck1

1 Department of Anatomy, University of Bern, Bern, Switzerland

* To whom correspondence should be addressed. E-mail: daepp{at}ana.unibe.ch.

This study investigated the use of the hindlimb suspension (HS) and reloading model of mice for the mapping of ultrastructural and gene expressional alterations underlying loaddependent muscular adaptations. Mice were hindlimb suspended for seven days or kept as controls (C, n=12). Soleus muscles were harvested after HS (HS7, n=23) or after resuming ambulatory cage activity (reloading) for either one (R1, n=13) or seven days (R7, n=9). Using electron microscopy, a reduction in mean fiber area (-37%) and in capillary-to-fiber ratio (from 1.83 to 1.42) was found for HS7. Subsequent reloading caused an increase in interstitial cells (+96%) and in total capillary length (+57%) while mean fiber area and capillary-to-fiber ratio did not significantly change compared to HS. Total RNA in the soleus muscle was altered with both HS (-63%) and reloading (+108% in R7 compared to C). This is seen as an important adaptive mechanism. Gene expression alterations were assessed by a muscle-specific low-density cDNA microarray. The transcriptional adjustments indicate an early increase of myogenic factors during reloading together with an overshoot of contractile (MyHC I and IIa) and metabolic (glycolytic and oxidative) mRNA amounts and suggest mechano-sensitivity of factors keeping the sarcomeres in register (desmin, titin, integrin {beta}1). Important differences to published data from former rat studies were found with the mouse HS model for contractile and glycolytic enzyme expression. These species-specific differences need to be considered when transgenic mice are used for the elucidation of monogenetic factors in mechano-dependent muscle plasticity.




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