2000 Fiscal Year Final Research Report Summary
Immunohistochemical investigation of copper transporting molecules in ALS model mice
| Project/Area Number |
11670623
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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 | Osaka University |
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Principal Investigator |
FUJIMURA Harutoshi Osaka University Graduate School of Medicine, Associate Professor, 医学系研究科, 助教授 (20263246)
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| Co-Investigator(Kenkyū-buntansha) |
KAIDO Misako Osaka University Hospital, Medical Staff, 医学部・附属病院, 医員
SAKODA Saburo Osaka University Graduate School of Medicine, Professor, 医学系研究科, 教授 (00178625)
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| Project Period (FY) |
1999 – 2000
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| Keywords | SOD1 / motor neuron disease / amyotrophic lateral sclerosis / transgenic mouse / copper chaperone / immunohistochemistry |
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| Research Abstract |
In order to lean about the effect of abnormal copper release from mutant SOD1 on the expression of copper trnasporting molecules, we investigated immunohistochemically ALS model mice. The antibodies against ATX-1, CCS, S100b, and methallothionein (MT) were adapted on the spinal cords from G93A mice at three different clinical phases (onset, progressive, and end stage). Throughout the course, ATX-1 and CCS were positive for the anterior horn cells, while MT was expressed in the entire astrocytes. It was noted that the most intense CCS immunoreactivity, associated with SOD1 immunoreactivity, was found in the Lewy body-like hyaline inclusions. The same immunoreactive pattern was also observed in the human autopsied cases with SOD1 related familial amyotrophic lateral sclerosis.
We crossed a G93A transgenic mice with MT knockout mice. The course of the double mutant mice resulted in a rapid progression, compared with wild G93A mice. In addition, astrocytosis was inadequately poor, correlated well with greater neuronal loss in this double mutant mice. These observations strongly supported the copper transport system is involved in the pathogenesis of motor neuron death in the mutant human SOD1 transgenic mice.
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