Instability of expressed Cu/Zn superoxide dismutase with 2 bp deletion found in familial amyotrophic lateral sclerosis

The mutant Cu/Zn superoxide dismutase (SODI) associated with familial amyotrophic lateral sclerosis (FALS) with a 2 bp deletion nas produced in two protein expression systems, The mutant SODI, expressed as a fusion protein in E. coli, had immunoreactivity to an anti-human SOD1 antibody but no SOD activity. It was more susceptible to proteolysis and its immunoreactivity decreased more rapidly than the wild type. The mutant SOD1, expressed in Cos1 cells, was not detected by either SOD activity staining or Western blot analysis, although expression of its mRNA aas confirmed. These results suggest that the mutant SOD1 is seriously unstable in mammalian cells.