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Functional analisis of invgene which determines lef-right axis and relates to renal development

Research Project

Project/Area Number 12671054
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Kidney internal medicine
Research InstitutionTokyo Woman's Medical University

Principal Investigator

TSUCHIYA Ken  Tokyo Woman's Medical University, Dept. Med., Asso. Prof., 医学部, 講師 (00246472)

Co-Investigator(Kenkyū-buntansha) MOCHIZUKI Toshio  Hokkaido University, School of Medicine, Associate Professor, 医学部, 講師 (00277120)
Project Period (FY) 2000 – 2002
Project Status Completed (Fiscal Year 2002)
Budget Amount *help
¥3,800,000 (Direct Cost: ¥3,800,000)
Fiscal Year 2002: ¥900,000 (Direct Cost: ¥900,000)
Fiscal Year 2001: ¥900,000 (Direct Cost: ¥900,000)
Fiscal Year 2000: ¥2,000,000 (Direct Cost: ¥2,000,000)
Keywordsleft-right axis / Situs inversus / Cystic kidney / knockout mouse / アンキリン / 左右決定 / モノクローナル抗体
Research Abstract

Vertebrate organisms have a common left-right asymmetry of their visceral organs. However, all unpaired organs of the chest and abdomen, such as heart, stomach, spleen and liver, develop from the midline in the fetus and localize to their normal positions in the adult. The mirror image reversal of this asymmetry is called situs inversus. The inversion of embryonic turning (tnv) mutation in a mouse was created by random insertional mutagenesis. The phenotype of the inv mouse is a consistent mirror-image reversal of the left-right polarity (situs inversus) and cystic formation of the kidneys. In previous project, we succeeded in cloning the whole sequence of mouse inv. As protein encoded by a candidate gene involved 15 consecutive repeats of ankyrin motif, there may be a possibility that a cytoskeletal abnormality was involved in the mechanism and production of structural abnormalities, inversion and cyst formation in the kidney. Based on the sequencing data, we had new results as to inv gene summarized below :
1) We succeeded in cloning the human inv gene and determined genomic organization, chromosomal mapping.
2) We modified mouse inv gene with some reporter genes, such as GFP protein or lacZ, and inserted into the expression vectors. We intend to use expression vector mounted whole mouse inv gene for transfection analysis in the culture cells.
3) We modified mouse inv gene with some reporter genes, such as GFP protein or lacZ, and excluded exon 1 to 2 for made up targeting vector for knockout mouse.

Report

(4 results)
  • 2002 Annual Research Report   Final Research Report Summary
  • 2001 Annual Research Report
  • 2000 Annual Research Report
  • Research Products

    (12 results)

All Other

All Publications (12 results)

  • [Publications] Mochizuki T, Tsuchiya et al.: "Molecular cloning of a gene for(inv) with cystic kidney"Nephrol Dial Transplant. 17.Sup9. 68-70 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Schen P, Tsuchiya et al.: "Identification, genomic organization, chromosomal mapping and mutation analysis of the human INV gene, the ortholog of a murine gene implicated in left-right axis development and biliary atresia"Hum Genet. 110. 157-165 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Tsuchiya et al.: "Mutation analysis 〜"Mut Res. 458. 583-590 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Ishii I, Tsuchiya K, Mochizuki T, Yokoyama T, Aikawa E, Nihei H: "Cyst-formed kidney in transgenic mice mutated in inversion of embryonic turning gene."Am J Pathol. (revised).

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Mochizuki T, Tsuchiya K, Yokoyama T: "Molecular cloning of a gene for inversion of embryo turning (inv) with cystic kidney."Nephrol Dial Transplant. 17 (suppl 9). 68-70 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Schon P, Tsuchiya K, Lenoir D, Mochizuki T, et al.: "Identification, genomic organization, chromosomal mapping and mutation analysis of the human INV gene, the orthology of a murine gene implicated in left-right axis development and biliary atresia."Hum Genet. 110. 157-165 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Tsuchiya K, Komeda M, Takahashi M, et al.: "Mutational analysis within the 3' region of the PKD1 gene in Japanese families."Mutat Res. 458(3-4). 583-590 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Imaki J, Onodera H, Tsuchiya K, et al.: "Developmental expression of maf- 1 messenger ribonucleic acids in rat kidney by in situ hybridization histochemistry."Biochem Biophys Res Commun. 272(3). 777-782 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Mochizuki T, Tsuchiya K et al.: "Molecular cloning of a gene for inv with cystic kidney"Nephrol Dial Transplant. 17,sup9. 68-70 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Schon P, Tsuchiya K et al.: "Identification, genenic organization〜"Hum Genet. 110. 157-165 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Tsuchiya K et al.: "Mutationanalysis〜"Mutat Res. 458. 583-590 (2001)

    • Related Report
      2002 Annual Research Report
  • [Publications] K.Tsuchiya et al: "Mutational analysis within the 3' region of the PKD1 gene in Japanese families"Mutat Res. 458. 77-84 (2001)

    • Related Report
      2001 Annual Research Report

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Published: 2000-04-01   Modified: 2016-04-21  

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