STRUCTURE AND DNA-SEQUENCE OF THE MOUSE MNSOD GENE

Oxidative damage to the cell has been implicated in the pathogenesis o f a number of disorders, including chronic inflammation, aging, and ca ncer. Manganese superoxide dismutase (MnSOD) plays a major role in the protection of the mitochondrion from oxidative damage due to superoxi de radicals and other excited oxygen species. In this report we descri be the genomic organization and DNA sequence of the murine MnSOD gene. This gene is interrupted by four introns. The coding sequence of this gene was examined in C57BL/6J and C3H/HeJ mice that are SUSCEPTIBLE a nd RESISTANT, respectively, to the pulmonary injuries induced by the i nhaled oxidants, ozone, and hyperoxia. Since the predicted amino acid sequence for MnSOD does not differ for these strains, nor does the siz e or steady-state level of this transcript, biologic variability in th e pulmonary inflammatory response to ozone acid hyperoxia does not ari se from an altered gene structure. Examination of the noncoding sequen ce revealed a dC . dA polymorphism in intron 2 and a StyI RFLV in intr on 4 of the MnSOD gene. These sequence and mapping data provide the ba sis for continued study of biologic variability in the MnSOD gene as a cause of disease.