Chronic hypoxia alters the level, maturation and control of gene expression in mouse kidney

Transcriptomic studies were undertaken to investigate the effect of hypoxia on kidney in early life to elucidate the genomic basis of renal injury and adaptation when oxygen is deprived. Fluorescently labeled, reverse-transcribed kidney RNA from 18 male and 18 female P2 mice, subjected for one, two or four weeks to normal atmospheric conditions (NAC) or to chronic constant (CCH) or intermittent (CIH) hypoxia were hybridized with 18 cDNA microarrays ("multiple yellow strategy", MYS). Expression level, stability, coordination and maturation of 1775 distinct genes were studied in each treatment-duration condition. Results: Both CIH and CCH change the expression level, stability and coordination of numerous genes that are involved in most major functional pathways. The fold change was significantly higher in female mice after one week of hypoxia and significantly higher in males after two and four weeks of hypoxia. Most solute carrier genes, including NHE1, are up-regulated and few down-regulated. There are genes coordinately expressed but others are much less so, with a remarkable overlap between the genes that are coexpressed in NAC and coregulated in CCH and CIH. Conclusion. Hypoxia is a major stress that alters the profile, stability and coordination of the kidney transcriptome in early life and slows down its maturation. Keywords: stress response Several litters of CD1 mice at P2 were split in nine groups and subjected for 1, 2 and 4 weeks to NAC (N), hypoxia in which [O2] was kept constant at 11% (CCH or C) and hypoxia in which [O2] was switched between 21% and 11% every four minutes (CIH or I). We have used the "multiple yellow strategy" (MYS) in which each slide was hybridized with Cy5-cDNA from the kidneys of one male mouse and Cy3-cDNA from the kidneys of one female mouse, both animals subjected to the same condition as described in Physiol Genomics. 22: 292-307. Data were processed as described in Physiol Genomics 20: 211-223, 2005.