Structure and DNA sequence of the mouse MnSOD gene.
Oxidative damage to the cell has been implicated in the pathogenesis of a number of disorders, including chronic inflammation, aging, and cancer. Manganese superoxide dismutase (Mn-SOD) plays a major role in the protection of the mitochondrion from oxidative damage due to superoxide radicals and other excited oxygen species. In this report we describe 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 AND RESISTANT, respectively, to the pulmonary injuries induced by the inhaled oxidants, ozone, and hyperoxia. Since the predicted amino acid sequence for MnSOD does not differ for these strains, nor does the size or steady-state level of this transcript, biologic variability in the pulmonary inflammatory response to ozone and hyperoxia does not arise from an altered gene structure. Examination of the noncoding sequence revealed a dC.dA polymorphism in intron 2 and a StyI RFLV in intron 4 of the MnSOD gene. These sequence and mapping data provide the basis for continued study of biologic variability in the MnSOD gene as a cause of disease.
DiSilvestre
D
D
Department of Environmental Health Sciences, Johns Hopkins Medical Institutions, Baltimore, Maryland 21287-7834, USA.
Kleeberger
S R
SR
Johns
J
J
Levitt
R C
RC
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D004198:Disease Susceptibility; D018496:Hyperoxia / Q000235:genetics; D007438:Introns; D008171:Lung Diseases / Q000235:genetics; D051379:Mice; D008809:Mice, Inbred C3H / Q000235:genetics*; D008810:Mice, Inbred C57BL / Q000235:genetics*; D008928:Mitochondria / Q000201:enzymology*; D008969:Molecular Sequence Data; D010126:Ozone / Q000633:toxicity; D016133:Polymerase Chain Reaction; D012150:Polymorphism, Restriction Fragment Length; D017422:Sequence Analysis, DNA; D013482:Superoxide Dismutase / Q000235:genetics*
D010126:Ozone; D013482:Superoxide Dismutase