| Budget Amount *help |
¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2012: ¥650,000 (Direct Cost: ¥500,000、Indirect Cost: ¥150,000)
Fiscal Year 2011: ¥520,000 (Direct Cost: ¥400,000、Indirect Cost: ¥120,000)
|
|---|
| Research Abstract |
Using the mouse strains G127TGGG (G127X), G85R, D90A, and G93A, which express SOD1 mutants with different copper-binding abilities, we showed that copper dyshomeostasis is common to these SOD1 mutants. Copper contents bound to the SOD1 active site varied considerably between SOD1 mutants: G93A and D90A SOD1 mutants have higher affinity to copper ions at their active site, whereas the affinity to copper ions are lower in G127X and G85R SOD1 mutants. Irrespective of the affinity, all the SOD1 mutants upregulated Steap2, Ctr1, Cox17, and Atox1, and downregulated Atp7a, which resulted in copper accumulation in spinal cords of the mice. We propose that copper dyshomeostasis is common to SOD1 mutation-linked ALS, and could be useful as a biological marker for the diagnosis.
|
