Transgenic Models for the Study of Lung Antioxidant Defense: Enhanced Manganese-containing Superoxide Dismutase Activity Gives Partial Protection to B6C3 Hybrid Mice Exposed to Hyperoxia

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Abstract
To investigate the role of manganese-containing superoxide dismutase (MnSOD) in lung antioxidant de- fense, lines of transgenic B6C3 hybrid mice carrying human MnSOD transgenes under the transcriptional control of a human b -actin promoter were established. Expression studies demonstrated that the human MnSOD transgene in line TgHMS66 is expressed and functional. The cellular distribution of the transgene product in the lungs was further examined by immunocytochemical analysis. Increased immunoreactive MnSOD was found in mitochondria of lung type I epithelial cells, type II epithelial cells, capillary endo- thelial cells, and fibroblasts. Furthermore, the magnitude of increase in mitochondrial labeling density of type II cells of nontransgenic, hemizygous, and homozygous transgenic littermates was proportional to the increased lung activity of MnSOD found in these mice. Transgenic mice over-expressing MnSOD did not have enhanced survival relative to controls when exposed to . 99% oxygen. However, when exposed to 90% oxygen, the transgenic mice had a small but statistically significant increase in survival time. Our re- sults indicate that when the b -actin promoter is used to increase activity of MnSOD it provides modest protection to B6C3 mice against hyperoxic lung injury. Ho, Y.-S., R. Vincent, M. S. Dey, J. W. Slot, and J. D. Crapo. 1998. Transgenic models for the study of lung antioxidant defense: enhanced manga- nese-containing superoxide dismutase activity gives partial protection to B6C3 hybrid mice exposed to hyperoxia. Am. J. Respir. Cell Mol. Biol. 18:538-547.