| Project/Area Number |
02670154
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| Research Category |
Grant-in-Aid for General Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Research Field |
Experimental pathology
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| Research Institution | Kyushu University |
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Principal Investigator |
IWAKI Toru Kyushu University, Faculty of Medicine, Lecturer, 医学部, 講師 (40221098)
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| Co-Investigator(Kenkyū-buntansha) |
TATEISHI Jun Kyushu University, Faculty of Medicine, Professor, 医学部, 教授 (70033305)
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| Project Period (FY) |
1990 – 1991
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| Project Status |
Completed (Fiscal Year 1991)
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| Budget Amount *help |
¥2,300,000 (Direct Cost: ¥2,300,000)
Fiscal Year 1991: ¥900,000 (Direct Cost: ¥900,000)
Fiscal Year 1990: ¥1,400,000 (Direct Cost: ¥1,400,000)
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| Keywords | alphaB-crystallin / Alexander's disase / Gene analysis / Transcriptional regulation / Heat shock protein / Immunohsitochemistry / αβークリスタリン / 転写調節 / 遺伝子構造 / アストログリア / ロ-ゼンタ-ル線維 / 免疫電顕法 |
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| Research Abstract |
AlphaB-crystallin, a major lens protein, is found in the central nervous system (CNS) and is a major protein component of Rosenthal fibers (RF), intracytoplasmic inclusions within astrocytes. Its level of expression in the normal CNS is low and appear to be confined to glial cells, both astrocytes and oligodendrocytes. A number of human brains displaying a variety of pathologic changes were examine by immunohistochemistry with an anti-alphaB-crystallin antiserum and increased immunoreactivity was found in astrocytes and oligodendrocytes without the formation of RFs. Furthermore, some neurons in neurodegenerative disorders were also immunolabeled with anti-alphaB-crystallin antiserum. Thus, the accumulation of Alpha B-crystallin appears to be part of the repertoire of reactive processes of CNS glial cells and some neurons in pathologic conditions.
We also determined the structures of alphaB-crystallin mRNAs and the genomic structure. Two major classes of mRNAs for the alphaB-crystallin, about 0.9 and 1.2 kilobases in length, are expressed in rat brain and they differ in the lengths of their 5' leader sequences. The transcriptional start sites of the longer mRNAs are preceded by a putative CAAT box and that of the shorter mRNA by a putative TATA box. Since there is only a single copy of the alphaB-crystallin gene, the two classes of mRNAs are generated by alternative transcriptional initiation from different promoters and their expressions are regulated differentially. Next, we examined primary structures of alphaB-crystallin in two cases of pathologically confirmed Alexander's disease. The genomic DNAs from frozen brain tissues were amplified by polymerase chain reaction and sequenced. Sequencing of the promoter and coding regions of the alphaB-crystallin genes in two patients revealed them to be of normal sequence, suggesting the accumulation of alphaB-crystallin in those brains is not due to any abnormality of the primary structure of the protein.
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