A speculative hypothesis about a gene dosage effect of Cu/Zn-superoxide dismutase in preventing toxic radical formation in the substantia nigra of DS patients is presented.
These results support the notion that CuZn SOD gene dosage effect could play a role in the pathogenesis of rapid aging features in the brain of Down's syndrome patients.
Cu,Zn superoxide dismutase (SOD-1) and glutathione peroxidase (GSHPx) activities were significantly elevated (1.39-fold and 1.24-fold, respectively) in DS individuals without AD.
DRG neurons which possessed additional copies of the gene for human superoxide dismutase-1 (SOD), a gene from the Down syndrome region of chromosome 21, were compared to normal neurons.
These findings suggest that CuZnSOD gene dosage is affecting the dense granule transport system and is thereby involved in the depressed level of blood serotonin found in patients born with Down's syndrome.
These data are consistent with the possibility that gene dosage of superoxide dismutase 1 contributes to oxygen metabolism modifications previously described in Down's syndrome.
These results indicate that the Down syndrome phenotype of this patient is due to microduplication of a chromosome 21 fragment containing the CuZn SOD gene.
These animals provide a unique system for studying the consequences of increased dosage of the Cu/Zn-superoxide dismutase gene in Down syndrome and the role of this enzyme in a variety of other pathological processes.
The erythrocyte superoxide dismutase-1 (SOD-1) was found to be normal, and so we conclude that SOD-1 excess is not necessarily observed in patients with Down's syndrome caused by partial 21 trisomy.
The gene locus for human cytoplasmic superoxide dismutase (SOD-1; superoxide:superoxide oxidoreductase, EC 1.15.1.1) is located in or near a region of chromosome 21 known to be involved in Down syndrome.
A child with characteristic clinical features of Down's syndrome and raised red cell SOD-1 activity was found to have, in addition to a single chromosome 21, a reverse dicentric tandem translocation of two No 21s with dual NORs and C band regions.
Because both IfRec and SOD-1 map to mouse chromosome 16, it will now be possible to use mice trisomic for this chromosome to determine whether certain aspects of the Down syndrome phenotype in man are caused by an altered dosage of IfRec and SOD-1.