EXTRACELLULAR-SUPEROXIDE DISMUTASE (SOD3) - TISSUE-SPECIFIC EXPRESSION, GENOMIC CHARACTERIZATION, AND COMPUTER-ASSISTED SEQUENCE-ANALYSIS OF THE HUMAN EC SOD GENE

We have isolated and characterized over 10,000 bp of the human EC SOD gene (SOD3 or EC 1.15.1.1) and its 5'- and 3'-fianking regions. Human genomic Southern blot analysis supports the existence of a single gene , without evidence for pseudogenes. The human EC SOD gene spans approx imately 5900 bp. The gene can be divided irate 3 exons and 2 introns. The 720-bp coding region is uninterrupted and located within exon 3. T he 560 bp 5' to the transcription start site were sequenced. No obviou s TATA box was identified. A variety of conserved cis elements were id entified by database searching. Exon 3 is surrounded by an Alu-J repet itive element in reverse orientation at the 5' and by an Alu-Sx repeti tive element in the 3'-flanking DNA. The relative levels of EC SOD tis sue-specific expression were determined by RNA gel blot analysis. Adul t heart, placenta, pancreas, and lung had the most expression, followe d by kidney, skeletal muscle, and liver. Little EC SOD message was fou nd in the brain. A second unique mRNA, approximately 4.2 kb in length, was highly expressed in skeletal muscle. When tissue enzyme activity is compared to relative mRNA levels, there is a marked disparity in th e brain, pancreas, and lung, suggesting that these tissues have enhanc ed affinity for circulating EC SOD or translate the EC SOD message mor e efficiently than other tissues. These results indicate that the EC S OD gene contains unique transcriptional regulatory elements and that i ts expression may be regulated at the post-transcriptional or post-tra nslational level. The characterization of the human EC SOD gene should now allow the development of further insights into its biology and pr ovide the basis for studies of its role in human heritable disorders. (C) 1994 Academic Press, Inc.