Plant & Animal Genomes XIII Conference Plant & Animal Genomes XIII ConferenceJanuary 15-19, 2005
Town & Country Convention Center
San Diego, CA
Mark R Band1 , Leonid Brodsky2 , Alma Joel2 , Eviatar Nevo2 , Aaron Avivi2
The blind subterranean mole rat of the Spalax ehrenbergi superspecies is an excellent model of hypoxic tolerance. Unique structural and functional modifications of the cardiovascular and respiratory systems including a high erythrocyte count and increased lung diffusion capacity allow survival at reduced oxygen tension. In contrast to Rattus, Spalax shows constitutively high levels of VEGF with increased capillary density and ability to respond to hypoxia with higher levels of erythropoietin. Likewise, functional differences were observed in molecules related to hypoxic tolerance such as hemoglobin, haptoglobin, myoglobin, neuroglobin and p53. Cross species gene expression analysis was performed using a mouse 15,000 gene cDNA microarray comparing global changes between Spalax and Rat exposed to normoxic or hypoxic conditions. Animals were exposed to ambient (20% O2) or hypoxic (6% O2) conditions for 6 hours. Comparisons between conditions were carried out individually for each species. Five tissues were analyzed, brain, muscle, liver, lung and heart. Over-expression of genes involved in apoptosis (Bnip3, Tia1), antioxidation (Hmox1, Cox8a), DNA repair (Xrcc1, Gadd45g), transcription (Klf9, Nr2f2), glycolysis (Ldh1, Tpi) and oxygen transport (Hba-a1) was observed among Rattus tissues, however few genes, with smaller effects, appear to change among Spalax samples. These results support the hypothesis that Spalax adaptation to fluctuating oxygen tension involves efficient regulation of key metabolic pathways critical to oxygen transport, including functional adaptations at the structural and molecular levels. Elucidation of these evolutionary changes and the potential for biomedical applications in ischemic syndromes will require further gene expression and large scale cDNA sequencing projects.