|Budget Amount *help
¥2,300,000 (Direct Cost : ¥2,300,000)
Fiscal Year 1994 : ¥1,000,000 (Direct Cost : ¥1,000,000)
Fiscal Year 1993 : ¥1,300,000 (Direct Cost : ¥1,300,000)
To investigate the possible role of oxygen free radicals in aging, antioxidant defense genes and mutants of the nematode C.elegans which are hypersensitive to oxygen were isolated. Then we tried to inject these genes into these oxygen-sensitive mutants to know their roles.
(1) We cloned a Mn-superoxide dismutase (SOD) gene
(2) An oxygen-sensitive mutant mev-1 has a short life span even under atmospheric condition and the life span changes depending on concentration of oxygen. This mutant has about half the wild-type level of Cu, Zn-SOD activity. The mev-1 mutant accumulated more fluorescent material at a greater rate than does wild type. Furthermore, the accumulation rates depended on concentration of oxygen. Since this phenotype has been widely used as an aging marker, these results suggested which mev-1 may be a mutant of premature aging.
(3) It has already been found a Cu, Zu-SOD (sod-1) on the chromosome II.
Recently, another Cu, Zu-SOD (sod-4) has been found on the chromosome III.The mev-1 gene may code the sod-4 itself because these genes are located at the same region on the chromosome III.By RT-PCR method, there were no difference in the mRNA level between the wild type and mev-1 mutant.
Microinjection of the sod-4 gene in the mev-1 mutants to know the role of the gene is in progress.
(4) Another oxygen-sensitive mutnat mev-3 of which development, fecundity and mean life span was retarded, reduced and shortened, respectively, when animals were incubated under high concentration of oxygen. Molecular cloning of the gene is in progress.