CLONING AND CHARACTERIZATION OF THE MURINE MANGANOUS SUPEROXIDE DISMUTASE-ENCODING GENE

The murine manganous superoxide dismutase-encoding gene (MnSOD) is hig hly homologous in both sequence and organization to its rat homolog. M nSOD is encoded by five exons spanning approx. 7 kb of DNA. RNA blot a nalysis indicated multiple RNA species, with the major RNA correspondi ng to a 960-bp message. This major transcript is highly inducible by t umor necrosis factor (TNF) in murine fibroblasts. Analysis of other mu rine tissues demonstrated ubiquitous expression. RNase protection and primer extension assays used to map the 5' end of the gene revealed a series of closely spaced multiple transcription start points, Sequence analysis of the 1.7 kb of 5' flanking DNA showed high homology to the 5' proximal 950 bp of the rat homolog. Within this region, multiple p otential regulatory elements are present, including several SP1 sites, two NF kappa B sites and an antioxidant-response element. However, no TATA box was identified, placing MnSOD in the family of inducible gen es that lack consensus TATA-box elements and contain G + C-rich promot er regions.