A new mouse model for temporal- and tissue-specific control of extracellular superoxide dismutase.
The extracellular isoform of superoxide dismutase (EC-SOD, Sod3) plays a protective role against various diseases and injuries mediated by oxidative stress. To investigate the pathophysiological roles of EC-SOD, we generated tetracycline-inducible Sod3 transgenic mice and directed the tissue-specific expression of transgenes by crossing Sod3 transgenic mice with tissue-specific transactivator transgenics. Double transgenic mice with liver-specific expression of Sod3 showed increased EC-SOD levels predominantly in the plasma as the circulating form, whereas double transgenic mice with neuronal-specific expression expressed higher levels of EC-SOD in hippocampus and cortex with intact EC-SOD as the dominant form. EC-SOD protein levels also correlated well with increased SOD activities in double transgenic mice. In addition to enabling tissue-specific expression, the transgene expression can be quickly turned on and off by doxycycline supplementation in the mouse chow. This mouse model, thus, provides the flexibility for on-off control of transgene expression in multiple target tissues.
Zou
Yani
Y
Department of Neurology and Neurological Sciences, Stanford University, Stanford, California, USA.
Chen
Chih-Hsin
CH
Fike
John R
JR
Huang
Ting-Ting
TT
D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology; D003433:Crosses, Genetic; D004318:Doxycycline / Q000494:pharmacology; D015971:Gene Expression Regulation, Enzymologic; D006624:Hippocampus / Q000201:enzymology; D008099:Liver / Q000201:enzymology; D051379:Mice; D008822:Mice, Transgenic; D008954:Models, Biological; D009928:Organ Specificity / Q000235:genetics; D018384:Oxidative Stress / Q000187:drug effects / Q000235:genetics; D013482:Superoxide Dismutase / Q000096:biosynthesis* / Q000235:genetics; D019076:Transgenes / Q000502:physiology*
D000900:Anti-Bacterial Agents; C499090:Sod3 protein, mouse; D013482:Superoxide Dismutase; D004318:Doxycycline