Targeted expression of human CuZn superoxide dismutase gene in mouse central nervous system.
Copper zinc superoxide dismutase (CuZnSOD) is an important enzyme for the detoxification of reactive oxygen species. Particularly in the central nervous system (CNS), reactive oxygen species are often associated with acute brain injuries and chronic neurodegeneration. It has been demonstrated in vivo that there is an inverse correlation between CuZnSOD activity and neuronal death after acute brain injury. To further understand the protective role of CuZnSOD upon neurons, we have generated transgenic mouse lines with targeted expression of the human CuZnSOD gene (SOD1) that is driven by a rat neuron-specific enolase gene promoter in neurons of the CNS. The transgenic SOD1 expression was restricted to the CNS identified by reverse transcriptase polymerase chain reaction and SOD gel electrophoresis assays. The CuZnSOD activity was significantly increased in the brain stem of the transgenic mice. Immunostaining of human CuZnSOD activity showed that Purkinje cells in the cerebellar cortex were the most intensely stained neurons in the CNS of the transgenic mice.
Li
Y
Y
Department of Neurological Surgery, University of California, School of Medicine, San Francisco 94143, USA.
Carlson
E
E
Murakami
K
K
Copin
J C
JC
Luche
R
R
Chen
S F
SF
Epstein
C J
CJ
Chan
P H
PH
D000818:Animals; D001921:Brain / Q000201:enzymology*; D001933:Brain Stem / Q000201:enzymology; D002531:Cerebellum / Q000201:enzymology; D015971:Gene Expression Regulation, Enzymologic; D006801:Humans; D007527:Isoenzymes / Q000096:biosynthesis / Q000235:genetics; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D009474:Neurons / Q000201:enzymology*; D010751:Phosphopyruvate Hydratase / Q000096:biosynthesis / Q000235:genetics; D011401:Promoter Regions, Genetic; D011689:Purkinje Cells / Q000201:enzymology; D051381:Rats; D011993:Recombinant Fusion Proteins / Q000096:biosynthesis; D015183:Restriction Mapping; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods; D013482:Superoxide Dismutase / Q000096:biosynthesis / Q000235:genetics*
D007527:Isoenzymes; D011993:Recombinant Fusion Proteins; D013482:Superoxide Dismutase; D010751:Phosphopyruvate Hydratase