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Analysis of Gene Array Changes in Muscle Caused by Spaceflight.  E.R. Bandstra1, J.L. Barth2, W.S. Argraves2 and T.A. Bateman1  1Dept. of Bioengineering, Clemson Univ., Clemson, SC. 2Dept. of Cell Biology and Anatomy, Medical Univ. of South Carolina, Charleston, SC.

   The microgravity of space has been shown to cause considerable atrophy in muscle.  Understanding and mitigating these changes is vital to accomplishing long term space exploration.  STS-108 was the first Space Shuttle flight with mice, providing a novel opportunity to exploit analysis tools optimized for this species.  Female C57BL/6J mice (64 days old) were separated into two groups: animal enclosure module (AEM- flight hardware housed) ground control and spaceflight (SF).  SF mice were exposed to microgravity for approximately 11 days and 19 hours on space shuttle Endeavour, December 2001.  Previously published work demonstrated a significant decrease in cross- sectional area of all muscle fiber types measured as well as a change in muscle fiber expression and decrease in citrate synthase activity in the gastrocnemius.  In order to determine the molecular and genetic root for these changes, microarray analysis was performed on the quadriceps of four SF and four AEM animals.  Using RMA reading and normalization methods with a 1.8 fold change and a false discovery rate of 1.5%, 103 genes were isolated.  In order to isolate genes specifically expressed in muscle tissue, microarray analysis was performed on the small intestine of four SF and four AEM animals.  RMA reading and normalization using 1.5 fold change and a false discovery rate of 5% revealed 26 genes that were differentially expressed in both muscle and gut tissue.  A thorough investigation of the literature on each of the 77 genes differentially expressed only in the muscle tissue was performed revealing several genes involved with muscle lineage and fiber type.  However, many genes were regulated in a way that would produce the opposite functional changes than those shown.  These results show that the time between reentry into gravity and sacrifice is long enough to produce gene expression changes related to the acclimation to 1g.  Further studies are necessary to determine the gene expression time pattern from disuse to loading.  (Supported by South Carolina Space Grant Consortium, NASA EPSCoR)