Generation of hypomorphic model mice utilizing an mRNA instability element
| Project/Area Number |
17500286
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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 |
Laboratory animal science
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| Research Institution | SHINSHU UNIVERSITY |
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Principal Investigator |
MORI Masayuki SHINSHU UNIVERSITY, Graduate School of Medicine, Associate Professor, 医学研究科, 助教授 (60273190)
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| Project Period (FY) |
2005 – 2006
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| Project Status |
Completed (Fiscal Year 2006)
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| Budget Amount *help |
¥3,500,000 (Direct Cost: ¥3,500,000)
Fiscal Year 2006: ¥1,300,000 (Direct Cost: ¥1,300,000)
Fiscal Year 2005: ¥2,200,000 (Direct Cost: ¥2,200,000)
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| Keywords | hypomorph / model mouse / mRNA instability element / 遺伝子 / ゲノム / 動物 |
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| Research Abstract |
We identified the genes associated with cataract formation in Shumiya cataract rat (SCR) by positional cloning. Mutations of the gene for lanosterol synthase (Lss) were identified. Cataract onset in SCR was uniquely regulated by a specific combination of different mutant (Lss^l) and polymorphic alleles (Lss^s) on the Lss locus. Lss^s was a hypomorphic allele with a G to A nucleotide substitution in exon 4. The G to A nucleotide substitution also caused instability of the Lss mRNA transcripts.
When a luciferase reporter gene was linked to the exon 4 sequence of Lss^s, which contain the mRNA instability element and expressed in the COS cells, luciferase activity was significantly reduced. This result indicated that the mRNA instability element functions regardless of the gene, in which it is located. We then examined the possibility that the change of an exonic splicing enhancer (ESE) element by the G to A substitution is the cause of instability of the Lss^s mRNA precursor. Analysis by the computer program ESEfinder identified a novel SRp40 binding motif, with a score of 4.15, in the Lss^s allele. SRp40 has previously been studied for its role in alternative splicing and has been shown to select both proximal and distal 5' splice sites in a substrate-specific manner. It was suggested that the Lss^s mRNA precursor becomes unstable if SRp40 splicing factor is bound to irrelevant sites in the precursor.
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Report
(3 results)
Research Products
(28 results)
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[Journal Article] Amyloidosis in transgenic mice expressing murine amyloidogenic apolipoprotein (Apoa2^c)2007
Author(s)
Ge F., Yao J., Fu X., Guo Z., Yan J., Zhang B., Zhang H., Tomozawa H., Miyazaki J., Sawashita J., Mori M., Higuchi K.
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Journal Title
Laboratory Investigations (印刷中)
Description
「研究成果報告書概要(和文)」より
Related Report
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[Journal Article] Lanosterol synthase mutations cause cholesterol deficiency-associated cataracts in the Shumiya cataract rat2006
Author(s)
Mori M., Li G., Abe I., Nakayama J., Guo Z., Sawashita J., Ugawa T., Nishizono S., Serikawa T., Higuchi K., Shumiya S.
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Journal Title
The Journal of Clinical Investigation 116・2
Pages: 395-404
Description
「研究成果報告書概要(和文)」より
Related Report
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[Journal Article] Lanosterol synthase mutations cause cholesterol deficiency-associated cataracts in the Shumiya cataract rat2006
Author(s)
Mori M., Li G., Abe I., Nakayama J., Guo Z., Sawashita J., Ugawa T., Nishizono S., Serikawa T., Higuchi K., Shumiya S.
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Journal Title
The Journal of Clinical Investigations 116(2)
Pages: 395-404
Description
「研究成果報告書概要(欧文)」より
Related Report
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[Journal Article] Lanosterol synthase mutations cause cholesterol deficiency-associated cataracts in the Shumiya cataract rat2006
Author(s)
Mori M., Li G., Abe I., Nakayama J., Guo Z., Sawashita J., Ugawa T., Nishizono S., Serikawa T., Higuchi K., Shumiya S.
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Journal Title
The Journal of Clinical Investigation 116(2)
Pages: 395-404
Related Report
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[Journal Article] Amyloidosis in transgenic mice expressing murine amyloidogenic apolipoprotein (Apoa2^c)
Author(s)
Ge F., Yao J., Fu X., Guo Z., Yan J., Zhang B., Zhang H., Tomozawa H., Miyazaki J., Sawashita J., Mori M., Higuchi K.
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Journal Title
Laboratory Investigations (in press)
Description
「研究成果報告書概要(欧文)」より
Related Report
