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Effects of Spaceflight on Hepatic Gene Expression in the C57BL/6 Mouse.  MJ Pecaut1, LM Green1, B Bianski1, TA Jones1, GA Nelson1, PJ Kostenuik6, TA Bateman3,4, S Morony5, LS Stodieck3, DL Lacey5, SJ Simske3, & DS Gridley1,2. Depts of 1Radiation Medicine (Radiobiology) and 2Biochem & Microbiol, Loma Linda Univ & Medical Center, Loma Linda, CA; Dept of 3Aerospace Engin, BioServe Space Technologies, Univ of Colorado at Boulder, Boulder, CO; 4Bioengineer Dept, Clemson Univ, Clemson, SC; and 5Amgen Inc, Thousand Oaks, CA.

The Space Shuttle Endeavor (STS-108/UF-1) launched for a 12-day mission on December 5th, 2001, allowing the first characterization of the effects of spaceflight on physiology in the C57BL/6 mouse model (FLT). Ground-based Animal Enclosure Module (AEM) and Vivarium (VIV) controls were housed on site at the National Aeronautics and Space Administration's (NASA) Life Sciences Support Facility (Hangar L) at the Cape Canaveral Air Force Station, Florida. Mice were euthanized and dissected within 3-5 hours of landing. Liver sections were immediately placed into cryovials, snap frozen in liquid nitrogen, and shipped to Loma Linda University where they were stored at —70C.  Tissue RNA was extracted in Trizol reagents and RNA quality was assessed. Although there were 12 animals/group (Pecaut et al, 2003; Gridley et al, 2003), we selected samples from 3 animals per group based on RNA purity (260/280 ratio) and degree of degradation (28s:18s ribosomal ratio). After extraction, aliquots of RNA were sent to the U of California at Irvine DNA & Protein MicroArray Facility for RNA processing and hybridization using the Affymetrix Mouse 430A gene chip. We limited our analysis to genes that consistently differed by two fold or greater when compared across groups. Of the 14,000+ genes evaluated, the expression of 61 genes decreased in FLT compared to VIV ground controls. Expression increased in 138 genes. In general, genes that enhanced TGF-induced apoptosis and cell differentiation, and inhibited inflammation, were up-regulated. These genes included jun, bcl6, caspase7, gadd45b, gadd45g, fkbp51, and tieg.  Not surprisingly, genes that enhanced inflammation and inhibited cell differentiation were down-regulated (i.e. lifr, irf-1, hsp25, hsp40, hsp70).

(Supported by NASA: Coop. Agreement NCC9-149 & Amgen Inc.)