| Project/Area Number |
17590347
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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 |
Experimental pathology
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| Research Institution | Shimane University |
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Principal Investigator |
HARADA Takayuki Shimane University, SCHOOL OF MEDICINE, DEPARTMENT OF PATHOLOGY, PROFESSOR (90112135)
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| Co-Investigator(Kenkyū-buntansha) |
OHIRA Akihiro SHIMANE UNIVERSITY, SCHOOL OF MEDICINE, DEPARTMENT OF OPHTHALMOLOGY, PROFESSOR (00169054)
NAKANO Akinobu SHIMANE UNIVERSITY, SCHOOL OF MEDICINE, DEPARTMENT OF PATHOLOGY, PROFESSOR (70263514)
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| Project Period (FY) |
2005 – 2007
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| Project Status |
Completed (Fiscal Year 2007)
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| Budget Amount *help |
¥3,740,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥240,000)
Fiscal Year 2007: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2006: ¥1,200,000 (Direct Cost: ¥1,200,000)
Fiscal Year 2005: ¥1,500,000 (Direct Cost: ¥1,500,000)
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| Keywords | CEREBELLAR ATAXIA / PURKINJYE CELL / APOPTOSIS / CASPASE / NEURAL CELL DEATH / AMS MOUSE / MUTANT / Nnal GENE / Nna1遺伝子 / プルキンエ細胞 / 神経細胞死 |
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| Research Abstract |
The Ataxia and Male Sterility (AMS) mouse is a mutant that exhibits ataxia due to a near-complete loss of the cerebellar Purkinje cells and male sterility because of severe oligospermia due to the degeneration and death of differentiating germ cells in the serniniferous tubules. The disease-responsible ams gene was shown to be allelic to Nnal, of which the biochemical function remains to be elucidated. A RT-PCR analysis to sequentially cover the whole transcript of the Nnal gene revealed that no obvious differences in either the size or quantity of the mRNA. By sequencing the cDNA base pairs a point mutation of .G to C was detected at 2423bp in exon 17. This missense mutation caused 808th arginie → proline and it appeared to affect the protein structure and stability, because the transfection of the cDNA construct of the wild-type, but not of the mutant, led to the translation and stable expression of the protein.
To investigate how ams mutation affects the cellular processes, we devote
… More
d our efforts to the morphological analysis of the mode of cell death. The causes of the acute pathological atrophy of the AMS cerebellum were not only the primary near complete loss of the Purkinje cells but also the secondary damage to other cells. Dying Purkinje cells lacked the characteristics of classical apoptosis, but in the granular layer typical apoptotic bodies were recognized by electron microscopy, and a substantial number of TUNEL-positive cells and activated caspase-3-positive cells were observed. Thus death of Purkinje cells appeared to be autonomous, whereas granule cell death was considered to be target-related apoptosis. Another study on:the photic injury of the photoreceptor cell of the AMS retina revealed that the cells had lost the ability to resist such injurious factors while, in addition, the process of apoptotic cell death was also different from that of classical apoptosis. Since the ams mutation affects the dying process of many cell types in different manners, Nnal is likely to act as an important regulator of the life of cells. Less
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