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Elucidation of molecular basis of May-Hegglin anomaly and its related disordes

Research Project

Project/Area Number 16390283
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Hematology
Research InstitutionNational Hospital Organization Nagoya Medical Center, Clinical Research Center

Principal Investigator

SAITO Hidehiko  National Hospital Organization Nagoya Medical Center, President, 名古屋医療センター, 院長 (20153819)

Co-Investigator(Kenkyū-buntansha) HAMAGUCHI Motohiro  National Hospital Organization Nagoya Medical Center, Clinical Research Center, Head, 臨床研究センター・止血血栓研究部, 部長 (30393177)
YAMAZAKI Tomio  National Hospital Organization Nagoya Medical Center, Clinical Research Center, Chief, 臨床研究センター・止血血栓研究部, 室長 (00282202)
KUNISHIMA Shinji  National Hospital Organization Nagoya Medical Center, Clinical Research Center, Chief, 臨床研究センター・止血血栓研究部, 室長 (60373495)
KOJIMA Tetsuhito  Nagoya University, Department of Medicine, Professor, 医学部, 教授 (40161913)
MATSUSHITA Tadashi  Nagoya University Hospital, Department of Hematology, Assistant Professor, 医学部附属病院, 助手 (30314008)
Project Period (FY) 2004 – 2005
Project Status Completed (Fiscal Year 2005)
Budget Amount *help
¥14,200,000 (Direct Cost: ¥14,200,000)
Fiscal Year 2005: ¥4,600,000 (Direct Cost: ¥4,600,000)
Fiscal Year 2004: ¥9,600,000 (Direct Cost: ¥9,600,000)
KeywordsMay-Hegglin anomaly / MYH9 disorders / NMMHCA / Congenital platelet disorders / Congenital thrombocytopenia / 血小板機能異常症 / 血小板減少症
Research Abstract

Analysis of MYH9 disorders
We studied the neutrophil NMMHCA localization in 10 patients with MYH9 disorders. In five cases, leukocyte inclusion bodies were observed on May-Grunwald-Giemsa stained peripheral blood smears. In the rest five cases, the presence of leukocyte inclusion bodies were ambiguous. Abnormal staining of neutrophil NMMHCA was detected in all cases. Subsequent mutational analysis of the MYH9 gene showed that all cases had a heterozygous MYH9 mutation. Immunofluorescence analysis of neutrophil NMMHCA localization represents a clear and unambiguous alternative to conventional staining for the detection of minute leukocyte inclusions and the diagnosis of the autosomal dominant macrothrombocytopenias caused by MYH9 mutations.
Establishment of MYH9 Knock in mice
Mouse genomic DNA clones were isolated from the 129SvJ-derived genomic library, and the clones spanning the exon 16 region were used to construct the targeting vector. A R702C point mutation was introduced by site-directed mutagenesis. At the 3' end, a LoxP-Neo-LoxP and DTA cassettes were inserted for positive and negative selection of electroporated ES cells, respectively. The targeting vector was electroporated to ES cells, and the homologous recombinants were selected by PCR and Southern blotting. The knock-in mice are under construction by crossing chimeric founders. After establishment of MYH9 R702C knock in mice, detailed pathohistological and physiological examinations of blood cells, kidney and inner ear will be investigated.

Report

(3 results)
  • 2005 Annual Research Report   Final Research Report Summary
  • 2004 Annual Research Report
  • Research Products

    (10 results)

All 2006 2005 2004 Other

All Journal Article (9 results) Book (1 results)

  • [Journal Article] Further characterization of anti-platelet monoclonal antibody HPL5 as anti-glycoprotein V antibody2006

    • Author(s)
      Kunishima S
    • Journal Title

      Acta Haematologica 115(1,2)

      Pages: 128-30

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Annual Research Report 2005 Final Research Report Summary
  • [Journal Article] Novel heterozygous missense mutation in the second leucine rich repeat of GPIbα affects GPIb/IX/V expression and results in macrothrombocytopenia in a patient initially misdiagnosed with idiopathic thrombocytopenic purpura2006

    • Author(s)
      Kunishima S
    • Journal Title

      European Journal of Haematology 76(4)

      Pages: 348-55

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Annual Research Report 2005 Final Research Report Summary
  • [Journal Article] Congenital macrothrombocytopenias2006

    • Author(s)
      Kunishima S
    • Journal Title

      Blood Reviews 20(2)

      Pages: 111-21

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Annual Research Report 2005 Final Research Report Summary
  • [Journal Article] Detection of unique neutrophil nonmuscle myosin heavy chain-A localization by immunofluorescence analysis in MYH9 disorder presented with macrothrombocytopenia without leukocyte inclusions and deafness2005

    • Author(s)
      Kunishima S
    • Journal Title

      Eur J Haematol 74・1

      Pages: 1-5

    • Related Report
      2004 Annual Research Report
  • [Journal Article] First description of somatic mosaicism in MYH9 disorders2005

    • Author(s)
      Kunishima S
    • Journal Title

      Br J Haematol 128・3

      Pages: 360-365

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Targeted disruption of mouse ortholog of the human MYH9 responsible for macrothrombocytopenia with different organ involvement : hematological, nephrological. and otological studies of heterozygous KO mice2004

    • Author(s)
      Matsushita T
    • Journal Title

      Biochem Biophys Res Commun 325・4

      Pages: 1163-1171

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Bernard-Soulier syndrome due to GPIX W127X mutation in Japan : Frequently misdiagnosed as idiopathic thrombocytopenic purpura

    • Author(s)
      Kunishima S
    • Journal Title

      International Journal of Hematology (in press)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Bernard-Soulier syndrome due to GPIX W127X mutation in Japan : frequently misdiagnosed as idiopathic thrombocytopenic purpura

    • Author(s)
      Kunishima S
    • Journal Title

      International Journal of Hematology (in press)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Bernard-Soulier syndrome due to GPIX W127X mutation in Japan : frequently misdiagnosed as idiopathic thrombocytopenic purpura

    • Author(s)
      Kunishima S
    • Journal Title

      International Journal of Hematology In press

    • Related Report
      2005 Annual Research Report
  • [Book] 図説血栓・止血・血管学 血栓症制圧のために2005

    • Author(s)
      國島伸治
    • Publisher
      中外医学社
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Annual Research Report 2005 Final Research Report Summary

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Published: 2004-04-01   Modified: 2016-04-21  

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