Analysis of repair systems for oxidative DNA damage in Senescence-Accelerated Mouso
| Project/Area Number |
11680819
|
|---|
| Research Category |
Grant-in-Aid for Scientific Research (C)
|
| Allocation Type | Single-year Grants |
|---|
| Section | 一般 |
|---|
| Research Field |
Laboratory animal science
|
|---|
| Research Institution | Shinshu University |
|---|
Principal Investigator |
MORI Masayuki School of Medicine, Shinshu University Lecturer, 医学部, 講師 (60273190)
|
|---|
| Co-Investigator(Kenkyū-buntansha) |
HIGUCHI Keiiti School of Medicine, Shinshu University Professor, 医学部, 教授 (20173156)
|
|---|
| Project Period (FY) |
1999 – 2000
|
| Project Status |
Completed (Fiscal Year 2000)
|
| Budget Amount *help |
¥3,700,000 (Direct Cost: ¥3,700,000)
Fiscal Year 2000: ¥1,400,000 (Direct Cost: ¥1,400,000)
Fiscal Year 1999: ¥2,300,000 (Direct Cost: ¥2,300,000)
|
|---|
| Keywords | accelerated senescence / oxidative stress / SAM / 8-oxoguanine / OGG1 / SAM / 8-OHdG |
|---|
| Research Abstract |
Senescence-Accelerated Mouse Prone (SAMP) strains, show accelerated senescence coupled with a short lifespan as a genetic trait, and hence are a useful animal model to elucidate the mechanisms involved in organismal senescence process. 8-Oxoguanine is one of the major premutagenic oxidative base legions in vivo and is suspected to play a crucial role in organismal senescence. Mammalian 8-oxoguanine DNA glycosylase (OGG1) is thought to play a major role in the removal of 8-oxoguanine adducts in vivo. We have assessed the possible implication of 8-oxoguanine and OGG1 and accelerated senescence and short lifespan of SAMP mice. Examination of the Ogg1 gene of SAM strains have revealed that all SAM strains, except for SAMR3, hold R336H substitution in the OGG1. In addition, all nine SAMP strains, but none of the five SAMR strains, had the R304W substitution. We have revealed that R304W mutation caused a complete loss of OGG1 activity, while the R336H mutation led to disruption of nuclear localization of the enzyme although the activity remained normal. We have also revealed that SAMP1 retained 1.5 to 1.9-fold increase in 8-oxoguanine level of hepatic nuclear DNA as compared with normal mice. until at least 12 months of age. A genetic association study utilizing two hybrid progenies originated from SAMP1 mice, however, indicated that the mutant Ogg1 gene per se is not responsible for the accelerated senescence and short lifespan of SAMP1. These data do not preclude the possibility that retention of the high 8-oxoguanine level is associated with accelerated senescence and short lifespan of SAMP1 mice. Further study utilizing SAMP1 mice might elucidate the possible implication of 8-oxoguanine in senescence.
|
Report
(3 results)
Research Products
(19 results)
