PHENOTYPIC RESCUE BY A BOVINE TRANSGENE IN A CU ZN SUPEROXIDE DISMUTASE-NULL MUTANT OF DROSOPHILA-MELANOGASTER/

Null mutants for Cu/Zn superoxide dismutase (CuZnSOD) in Drosophila me lanogaster are male sterile, have a greatly reduced adult life span, a nd are hypersensitive to paraquat. We have introduced a synthetic bovi ne CuZnSOD transgene under the transcriptional control of the D. melan ogaster 5C actin promoter into CuZnSOD-null mutant of D. melanogaster. This was carried out by P-element-mediated transformation of the Dros ophila-bovine CuZnSOD transgene into a CuZnSOD+ recipient strain follo wed by genetic crossing of the transgene into a strain carrying the Cu ZnSOD-null mutation, CSODn108. The resulting transformants express bov ine CuZnSOD exclusively to about 30% Of normal Drosophila CuZnSOD leve ls. Expression of the Drosophila-bovine CuZnSOD transgene in the CuZnS OD null mutant rescues male fertility and resistance to paraquat to ap parently normal levels. However, adult life spae is restored to only 3 0% of normal, and resistance to hyperoxia is 90% of that found in cont rol flies. This striking differential restoration of pleiotropic pheno types could be the result of a threshhold of CuZnSOD expression necess ary for normal male fertility and resistance to the toxicity of paraqu at or hyperoxia which is lower than the threshold required to sustain a normal adult life span. Alternatively, the differential rescue of fe rtility, resistance to active oxygen, and life span might indicate dif ferent cell-specific transcriptional requirements for these functions which are normally provided by the control elements of the native CuZn SOD