Contribution of iNOS for neurodegeneration in ALS and Parkinson's disease
| Project/Area Number |
12670629
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Neurology
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| Research Institution | Kansai Medical University |
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Principal Investigator |
ITO Hidefumi Kansai Medical University Faculty of Medicine Associate Professor, 医学部, 助教授 (20250061)
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| Co-Investigator(Kenkyū-buntansha) |
ITO Seiji Kansai Medical University Faculty of Medicine Professor, 医学部, 教授 (80201325)
NISHIZAWA Mikio Kansai Medical University Faculty of Medicine Assistant Professor, 医学部, 講師 (40192687)
KUSAKA Hirofumi Kansai Medical University Faculty of Medicine Professor, 医学部, 教授 (70250066)
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| Project Period (FY) |
2000 – 2001
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| Project Status |
Completed (Fiscal Year 2001)
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| Budget Amount *help |
¥2,900,000 (Direct Cost: ¥2,900,000)
Fiscal Year 2001: ¥1,200,000 (Direct Cost: ¥1,200,000)
Fiscal Year 2000: ¥1,700,000 (Direct Cost: ¥1,700,000)
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| Keywords | iNOS / SOD1 / ALS / knockout mouse / transgeneic mouse / 交配実験 / superoxide dismutase / nitric oxide synthese / amyotrophic lateral sclerosis / Parkinson / transgenic nouse |
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| Research Abstract |
To investigate the roles of inducible nitric oxide synthase (iNOS) for neuronal cell degeneration in amyotrophic lateral sclerosis (ALS), we have attempted to cross iNOS knockout (iNOS -/-) mouse with mutant SOD1 transgenic (m SOD1 Tg/W) mouse. For this purpose, we purchased the B6SJL-TgN(SOD1-G93A)1Gur strain and the B6.129P2-Nos2tm1Lau strain from The Jackson Laboratory, USA. After observation of motor functions, life span, and fertility of each mouse for 3 generations, we crossed male mSOD1 Tg/W mice with female iNOS -/- mice. Successfully generated male mSOD1 Tg/W II iNOS +/- mice were re-crossed with female mSOD1 W/W II iNOS +/- mice. Through these procedures we finally obtained genetically different 6 groups of the mice; mSOD1 Tg/W II iNOS -/-, mSOD1 Tg/W II iNOS +/-, mSOD1 Tg/W II iNOS +/+, mSOD1 W/W II iNOS -/-, mSOD1 W/W II iNOS +/-, mSOD1 W/W II iNOS +/+. Eight to 12 mice from each genotype group were randomly selected and their motor functions were closely observed until the day when each mSOD1 Tg/W mouse was unable to eat and drink. The observers were blinded for genotypes of the mice. Motor functions were evaluated by clinical examination, by body weight, and by grasping power and the remaining time on the Rotarod. Significant differences were demonstrated between mSOD1 Tg/W II iNOS +/+ and mSOD1 Tg/W II iNOS +/-, and between mSOD1 Tg/W II iNOS +/+ and mSOD1 Tg/W II iNOS -/-; deterioration of motor function was significantly earlier in the latter 2 groups than the former one. These results imply that iNOS might play protective roles in processes of neurodegeneration in m SOD1 Tg/W mouse.
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Report
(3 results)
Research Products
(10 results)
