Comparison of gene expression in whole blood of mice subjected to normobaric hypoxia in vivo

To determine hypoxia mediated changes in whole blood, normal C57Bl/10 mice were gradually exposed to a chronic hypoxic environment, equivalent to an altitude of 6500m, for 2 weeks in vivo. Control, age-matched mice were maintained under normoxic, normobaric conditions by exposing them to ambient air in Philadelphia (c. 50 mts above sea level). Purpose: To determine the expression profile of genes differentially expressed in mouse whole blood upon exposure to normobaric hypoxia in vivo. Methods: The hypoxic group consisting of 6 C57/BL10 mice was exposed to normobaric hypoxia, in a specially designed and hermetically closed hypoxic chamber, using a gas mixing system Pegas 4000 MF (Columbus Instruments, Ohio, USA). The oxygen level was decreased from 21% to 8% over a period of 14 days. 6 control mice were kept at normal oxygen and pressure levels by exposing them to ambient air in Philadelphia (c. 50 mts above sea level). RNA from whole blood was isolated, processed and used for microarray-based expression profiling. Profiles were generated for genes differentially expressed at control versus normobaric hypoxia in whole blood using a false discovery rate (FDR) of 0%. The Profile was validated by real-time quantitative reverse transcription-polymerase chain reaction (qPCR) on 2 biologically independent samples, not used for generating the profile. Results: The transcriptomes associated with normobaric hypoxia in whole blood were identified. We found 4723 genes that were differentially expressed in normobaric hypoxic whole blood compared to control with a 0% FDR and a 2 fold cutoff. Conclusion: Transcriptome level differences exist in the whole blood of animals subjected to normobaric hypoxia. Our definition of the normobaric hypoxia blood transcriptome provides insight into the functioning and response to hypoxia in whole blood.