• Search Research Projects
  • Search Researchers
  • How to Use
  1. Back to previous page

Generation of hypomorphic model mice utilizing an mRNA instability element

Research Project

Project/Area Number 17500286
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Laboratory animal science
Research InstitutionSHINSHU UNIVERSITY

Principal Investigator

MORI Masayuki  SHINSHU UNIVERSITY, Graduate School of Medicine, Associate Professor, 医学研究科, 助教授 (60273190)

Project Period (FY) 2005 – 2006
Project Status Completed (Fiscal Year 2006)
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)
Keywordshypomorph / model mouse / mRNA instability element / 遺伝子 / ゲノム / 動物
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.

Report

(3 results)
  • 2006 Annual Research Report   Final Research Report Summary
  • 2005 Annual Research Report
  • Research Products

    (28 results)

All 2007 2006 2005 Other

All Journal Article (28 results)

  • [Journal Article] Functional polymorphisms of the Lss and Fdftl genes in laboratory rats2007

    • Author(s)
      Mori M., Sawashita J., Higuchi K.
    • Journal Title

      Experimental Animals 56・2

      Pages: 93-101

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Quantitative trait locus that determines the cross-sectional shape of the femur in SAMP6 and SAMP2 mice2007

    • Author(s)
      Otsuki B., Matsumura T., Shimizu M., Mori M., Okudaira S., Nakanishi R., Higuchi K., Hosokawa M., Tsuboyama T., Nakamura T.
    • Journal Title

      Journal of Bone and Mineral Research 22・5

      Pages: 675-685

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Annual Research Report 2006 Final Research Report Summary
  • [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.
    • Journal Title

      Laboratory Investigations (印刷中)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Functional polymorphisms of the Lss and Fdft1 genes in laboratory rats2007

    • Author(s)
      Mori M., Sawashita J., Higuchi K.
    • Journal Title

      Experimental Animals 56(2)

      Pages: 93-101

    • NAID

      130000068039

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Quantitative trait locus that determines the cross-sectional shape of the femur in SAMP6 and SAMP2 mice2007

    • Author(s)
      Otsuki B., Matsumura T., Shimizu M., Mod M., Okudaira S., Nakanishi R., Higuchi K., Hosokawa M., Tsuboyama T., Nakamura T.
    • Journal Title

      Journal of Bone and Mineral Research 22(5)

      Pages: 675-685

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Functional polymorphisms of the Lss and Fdftl genes in laboratory rats.2007

    • Author(s)
      Mori M., Sawashita J., Higuchi K.
    • Journal Title

      Experimental Animals 56・2

      Pages: 93-101

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Reduced Coenzyme Q10 supplementation decelerates senescence in SAMP1 mice2006

    • Author(s)
      Yan J., Fujii K., Yao J., Kishida H., Hosoe K., Sawashita J., Takeda T., Mori M., Higuchi K.
    • Journal Title

      Experimental Gerontology 41・2

      Pages: 130-140

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [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.
    • 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
      2006 Final Research Report Summary
  • [Journal Article] Transmission of amyloidosis in offspring of mice with AApoAII amyloidosis2006

    • Author(s)
      Korenaga T., Yan J., Sawashita J., Matsushita T., Naiki H., Hosokawa M., Mori M., Higuchi K., Fu X.
    • Journal Title

      American Journal of Pathology 168・3

      Pages: 898-906

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Transmissibility of mouse AApoAII amyloid fibrils : inactivation by physical and chemical methods2006

    • Author(s)
      Zhang H., Sawashita J., Fu X., Korenaga T., Yan J., Mori M., Higuchi K.
    • Journal Title

      FASEB Journal 20・7

      Pages: 1012-1014

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] A third locus for eosinophilia on chromosome 1 of the MES rats2006

    • Author(s)
      Mori M., Higuchi K., Matsumoto K.
    • Journal Title

      Experimental Animals 55・5

      Pages: 497-500

    • NAID

      130000068084

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Secreted Frizzled-Related Protein 4 as a negative regulator of bone formation and a candidate gene affecting peak bone mineral density in mice2006

    • Author(s)
      Nakanishi R., Shimizu M., Mori M., Akiyama H., Otsuki B., Okudaira S., Hashimoto M., Higuchi K., Tsuboyama T., Nakamura T.
    • Journal Title

      Journal of Bone and Mineral Research 21・11

      Pages: 1713-1721

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Reduced Coenzyme Q10 supplementation decelerates senescence in SAMP1 mice2006

    • Author(s)
      Yan J., Fujii K., Yao J., Kishida H., Hosoe K., Sawashita J., Takeda T., Mod M., Higuchi K.
    • Journal Title

      Experimental Gerontology 41(2)

      Pages: 130-140

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [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.
    • 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
      2006 Final Research Report Summary
  • [Journal Article] Transmission of amyloidosis in offspring of mice with AApoAII amyloidosis2006

    • Author(s)
      Korenaga T., Yan J., Sawashita J., Matsushita T., Naiki H., Hosokawa M., Mod M., Higuchi K., Fu X.
    • Journal Title

      American Journal of Pathology 168(3)

      Pages: 898-906

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Transmissibility of mouse AApoAII amyloid fibrils: inactivation by physical and chemical methods2006

    • Author(s)
      Zhang H., Sawashita J., Fu X., Korenaga T., Yan J., Mori M., Higuchi K.
    • Journal Title

      FASEB Journal 20(7)

      Pages: 1012-1014

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] A third locus for eosinophilia on chromosome 1 of the MES rats2006

    • Author(s)
      Mori M., Higuchi K., Matsumoto K.
    • Journal Title

      Experimental Animals 55(5)

      Pages: 497-500

    • NAID

      130000068084

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Secreted Frizzled-Related Protein 4 as a negative regulator of bone formation and a candidate gene affecting peak bone mineral density in mice2006

    • Author(s)
      Nakanishi R., Shimizu M., Mori M., Akiyama H., Otsuki B., Okudaira S., Hashimoto M., Higuchi K., Tsuboyama T., Nakamura T.
    • Journal Title

      Journal of Bone and Mineral Research 21(11)

      Pages: 1713-1721

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Transmissibility of mouse AApoAII amyloid fibrils : inactivation by physical and chemical methods.2006

    • Author(s)
      Zhang H., Sawashita J., Fu X., Korenaga T., Yan J., Mori M., Hifuchi K.
    • Journal Title

      FASEB Journal 20・7

      Pages: 1012-1014

    • Related Report
      2006 Annual Research Report
  • [Journal Article] A third locus for eosinophilia on chromosome 1 of the MES rats.2006

    • Author(s)
      Mori M., Higuchi K., Matsumoto K.
    • Journal Title

      Experimental Animals 55・5

      Pages: 497-500

    • NAID

      130000068084

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Secreted Frizzled-Related Protein 4 as a negative regulator of bone formation and a candidate gene affecting peak bone mineral density in mice.2006

    • Author(s)
      Nakanishi R., Shimizu M., Mori M., Akiyama H., Otsuki B., Okudaira S., Hashimoto M., Higuchi K., Tsuboyama T., Nakamura T.
    • Journal Title

      Journal of Bone and Mineral Research 21・11

      Pages: 1713-1721

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Reduced Coenzyme Q10 supplementation decelerates senescence in SAMP1 mice2006

    • Author(s)
      Yan J., Fujii K., Yao J., Kishida H., Hosoe K., Sawashita.J., Takeda T., Mori M., Higuchi K.
    • Journal Title

      Experimental Gerontology 41(2)

      Pages: 130-140

    • Related Report
      2005 Annual Research Report
  • [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.
    • Journal Title

      The Journal of Clinical Investigation 116(2)

      Pages: 395-404

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Transmission of amyloidosis in offspring of mice with AApoAII amyloidosis2006

    • Author(s)
      Korenaga T., Yan J., Sawashita J., Matsushita M., Naiki H., Hosokawa M., Mori M., Higuchi K., Fu X.
    • Journal Title

      American Journal of Pathology 168(3)

      Pages: 898-906

    • Related Report
      2005 Annual Research Report
  • [Journal Article] A locus for eosinophilia in the MES rat is on chromosome 192005

    • Author(s)
      Li G., Guo Z., Higuchi K., Kawakubo M., Matsumoto K., Mori M.
    • Journal Title

      Mammalian Genome 16・7

      Pages: 516-523

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] A locus for eosinophilia in the MES rat is on chromosome 192005

    • Author(s)
      Li G., Guo Z., Higuchi K., Kawakubo M., Matsumoto K., Mod M.
    • Journal Title

      Mammalian Genome 16(7)

      Pages: 516-523

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] A locus for eosinophilia in the MES rat is on Chromosome 192005

    • Author(s)
      Li G., Guo Z., Higuchi K., Kawakubo M., Matsumoto K., Mori M.
    • Journal Title

      Mammalian Genome 16(7)

      Pages: 516-523

    • Related Report
      2005 Annual Research Report
  • [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.
    • Journal Title

      Laboratory Investigations (in press)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary

URL: 

Published: 2005-04-01   Modified: 2016-04-21  

Information User Guide FAQ News Terms of Use Attribution of KAKENHI

Powered by NII kakenhi