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 fu sion protein in E. coli, had immunoreactivity to an anti-human SOD1 an tibody but no SOD activity. It was more susceptible to proteolysis and its immunoreactivity decreased more rapidly than the wild type. The m utant SOD1, expressed in Cos1 cells, was not detected by either SOD ac tivity staining or Western blot analysis, although expression of its m RNA aas confirmed. These results suggest that the mutant SOD1 is serio usly unstable in mammalian cells.