Unknown,Transcriptomics,Genomics,Proteomics

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Systems genetics approach to low dose radiation sensitivity in BXD recombinant inbred mice

ABSTRACT: The immune system illustrates the challenges of assigning risk to low dose radiation (LDR) exposure in a population. While high radiation doses clearly suppress immune function, a number of studies have shown that LDR affects immune cell subpopulations in ways that could be beneficial. In the intact organism, defining the consequences of LDR is further complicated by the impact of genetic background, particularly in systems such as the immune system for which both radiosensitivity and genetic effects are profound. We employed a systems genetics approach to test for heritable differences in LDR responses. Mice from 39 BXD recombinant inbred (RI) strains were exposed to 10cGy gamma radiation to determine effects on immune function and oxidative stress 48h after irradiation. LDR significantly enhanced neutrophil phagocytosis in a manner that was independent of genetic background. In contrast, genetic background significantly impacted LDR-induced changes in spleen superoxide dismutase activity. Transcriptome data from spleens of the BXD parental strains highlighted the impact of genetic background on LDR responses and also indicate that genetic variation in radiosensitivity is further unmasked at low radiation doses. Taken together, these data highlight the need to consider genetic variation when assessing LDR outcomes. Adult C57BL/6J and DBA/2J mice (10 weeks old) were exposed to low dose (10cGy) or high dose (1Gy) gamma radiation. Mice were sacrificed 24h after radiation or sham exposure & spleens were harvested for transcriptomic analysis.

ORGANISM(S): Mus musculus

SUBMITTER: Rachel Lynch

PROVIDER: E-GEOD-21562 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Project description:Although radiation effects have been extensively studied, the biological effects of low-dose radiation (LDR) are controversial. This study investigates LDR-induced alterations in locomotive behavior and gene expression profiles of Drosophila melanogaster. We measured locomotive behavior using larval pupation height and rapid iterative negative geotaxis (RING) assay after exposure to 0.1 Gy gamma-radiation (dose rate of 16.7 mGy/h). We also observed chronic LDR effects on development (pupation and eclosion rates) and longevity (life span). To identify chronic LDR effects on gene expression, we performed whole-genome expression analysis using gene-expression microarrays, and confirmed the results using quantitative real-time PCR. Pupation height was significantly higher after LDR treatment at the first larval instar. Locomotive behavior of male flies was significantly greater approximately 3M-BM--5 weeks after LDR, but pupation and eclosion rates and life spans were not significantly different. Genome-wide expression analysis identified 344 genes that were differentially expressed in irradiated larvae compared with those of controls. We identified several genes belonging to larval behavior functional groups such as locomotive behavior and oxidation reduction, and genes involved in conventional functional groups modulated by irradiation such as defense response, sensory and perception. Four candidate genes were confirmed as differentially expressed genes in irradiated larvae using qRT-PCR. These data suggest that LDR stimulates locomotion-related genes, and these genes can be used as potential markers for LDR. Eggs were collected from 5-day-old female flies and cultivated for 24 h on standard medium. Then, twenty larvae were manually selected and seeded on fresh standard medium in a new vial. After transfer, the experimental group of first-instar larvae was immediately irradiated with chronic gamma-radiation at a dose rate of 16.7 mGy/h. After treatment, gamma-irradiated flies and non-irradiated control flies were maintained in the same incubator at 25degC.

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Systems genetics approach to low dose radiation sensitivity in BXD recombinant inbred mice

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