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MICRO-GRAVITY EXPOSURE RESULTS IN SIGNIFICANT ATROPHY OF MURINE SKELETAL MUSCLE WITHOUT ALTERATIONS IN MYOSIN HEAVY CHAIN GENE EXPRESSION.   B.C. Harrison¹, D.L. Allen¹, L.S. Stodieck², P.J. Kostenuik³, T.A. Bateman², S. Morony³ and L.A. Leinwand¹.  ¹Molecular, Cellular, and Developmental Biology, University of Colorado, Boulder, ²BioServe Space Technologies, University of Colorado, Boulder, and ³Amgen, Inc., Thousand Oaks CA.

   The purpose of this study was to investigate the effects of micro-gravity on murine skeletal muscle fiber size and myosin heavy chain (MyHC) isoform expression.  As part of a larger study, female C57BL/6J mice, aged 64 days were divided into Animal Enclosure Module ground control (AEM) and Space Flight (SF).  SF animals were flown on the Space Shuttle Endeavour (STS-108/UF-1) and subjected to 11 days and 17 hours of micro-gravity.  Following the shuttle flight, both AEM control and SF animals were sacrificed, and the triceps surae (gastrocnemius, plantaris, and soleus) of each animal was dissected and frozen in liquid nitrogen-cooled isopentane.  Immunohistochemical analysis of muscle fiber cross-sectional area (CSA) revealed that, in each of the muscles analyzed, mean muscle fiber CSA was significantly reduced (p < 0.0001) for all fiber types for SF versus AEM control.  In the gastrocnemius, mean CSA was reduced by 29%, 35%, 15%, and 18% for type I, type IIA, type IIX, and type IIB fibers, respectively.   In the plantaris, fiber CSA decreased by 22%, 20%, and 16% for types IIA, IIX, and IIB, respectively.  In the soleus, type I CSA was reduced by micro-gravity exposure 31% while type IIA CSA was reduced by 26%.  Immunohistochemical analysis of MyHC isoform expression revealed no significant change in the percentage of fibers expressing MyHC-I, -IIa, -IId/x, or –IIb across analyzed muscles.  Overall, these data indicate that, in the mouse, exposure to micro-gravity results in significant muscle fiber atrophy.  Furthermore, this muscle fiber atrophy is more pronounced in oxidative muscle fibers (Type I and IIA) than in glycolytic muscle fibers (Type IIX and IIB).  Contrary to previously observed results in the rat, monkey, and human, however, micro-gravity exposure does not significantly alter MyHC isoform expression in mouse skeletal muscle.

(Supported by NIH GM 29090 to LAL)

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