| Project/Area Number |
13671862
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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 |
Ophthalmology
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| Research Institution | INSTITUTE FOR DEVELOPMENTAL RESEARCH, AICHI HUMAN SERVICE CENTER. |
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Principal Investigator |
MASAKI Shigeo INSTITUTE FOR DEVELOPMENTAL RESEARCH, AICHI HUMAN SERVICE CENTER., Department of Embryology, Senior Researcher, 発達障害学部, 主任研究員 (10157175)
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| Co-Investigator(Kenkyū-buntansha) |
QUINLAN Roy University of Durham, Department of Biological Sciences, Professor, 生化学部, 教授
ITO Yoshimasa Kinki University, School of Pharmaceutical Sciences, Assistant Professor, 薬・製剤学, 助教授 (50128633)
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| Project Period (FY) |
2001 – 2003
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| Project Status |
Completed (Fiscal Year 2003)
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| Budget Amount *help |
¥1,500,000 (Direct Cost: ¥1,500,000)
Fiscal Year 2003: ¥500,000 (Direct Cost: ¥500,000)
Fiscal Year 2002: ¥1,000,000 (Direct Cost: ¥1,000,000)
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| Keywords | cataract / filensin / tissue specific expression / cell differentiation / transcription factor / gamma crystallin / amyloid / lens / 組織特異的発現 / 発現異常 |
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| Research Abstract |
1.Lens fiber cell specific expression machinery and the transcriptsome analysis for filensin gene. We have isolated mouse filensin gene promoter, and constructed a set of reporter plasmids with each different 10 bp deleted sequences between 56/93 of filensin promoter. Among these, four plasmids have lost promoter activity indicating a region corresponding to deleted sequences reacts to some transcription factors for filensin gene expression. Then we have tried to identify such transcription factors by EMSA and oligomer conjugated column chromatography using with double stranded oligomers for deleted sequences. Sp1 and some factors were identified. Functional analysis of filensin deficient knockout mouse.
2.The knockout mouse was produced in order to explore the function of lens filensin. Since the abnormalities were not observed appearance, we are now investigating for fine eye disorganization under the microscopy.
3.Hereditary cataract caused by mutated gamma crystallins. As three different kinds of mouse heredity cataracts by gamma crystallin gene mutation are known. Until now it was unclear the mechanism how mutated gamma crystallin cause the cataract symptoms. In the lens fiber cell nuclei from three kinds of each mutant mouse, amyloid like inclusions were seen. Recombinant mutated gamma crystallin formed amyloid like structure in vitro. These results indicated that gamma crystallins form nuclear inclusion by the mutation and these disrupt and decrease nuclear function, then cause inherited cataract in mouse lens.
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