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Role of calcium signals for metabolic syndromes in children.

Research Project

Project/Area Number 16591042
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Pediatrics
Research InstitutionKumamoto University

Principal Investigator

NAKAMURA Kimitoshi  Kumamoto University, Hospital, Pediatrics, Assistant Professor, 医学部附属病院, 助手 (30336234)

Project Period (FY) 2004 – 2005
Project Status Completed (Fiscal Year 2005)
Budget Amount *help
¥3,600,000 (Direct Cost: ¥3,600,000)
Fiscal Year 2005: ¥1,400,000 (Direct Cost: ¥1,400,000)
Fiscal Year 2004: ¥2,200,000 (Direct Cost: ¥2,200,000)
Keywordscalcium / metabolic syndrome / dyslipidemia / transgenic mice / hepatocytes / 不整脈
Research Abstract

Calreticulin (CRT) is a Ca^<2+>-binding protein of the endoplasmic reticulum and essential for cardiac development. Cardiac specific overexpression of calreticulin by α-myosin heavy chain promoter results in complete heart block and sudden death in transgenic mice. For further investigating mechanism of calreticulin in cardiac development and its function, we generate transgenic mice that cause temporal and spatial overexpression of calreticulin using cre-loxP system. By microinjection of the transgene which contains a CAG promotor, a loxP-flanked chloramphenicol acetyltransferas (CAT) gene, and CRT cDNA into pronuclear cells of C57BL/6 mice, we made loxP-CRT transgenic mice. The mice were cross-bred with Nkx2.5-Cre mice which express cre recombinase under control of Nkx2.5 promoter, a transcription factor essential for early cardiac development. The breeding were resulted in transgenic mice with cardiac specific overexpression of calreticulin (Nkx2.5-CRT transgenic mice). Cardiac calreticulin protein levels of Nkx2.5-CRT transgenic mice were increased by 44-fold compared with control mice. Overexpression of calreticulin was associated with PR interval, QRS interval prolongation, bradycardia, and sudden death observed from 6- to 10-week-old. Furthermore, some NKx2.5-CRT transgenic mice revealed marked edema in 7-week-old. RT-PCR analysis revealed that the expression of hyperpolerization-activated cyclic nucleotide-gated channel1 (HCN1), essential component for cardiac pace maker activity, was receded in the heart of Nkx2.5-CRT transgenic mice. These suggested that carleticulin affect cardiac arrhythmia with disruption of cardiac signaling, such as HCN families. In conclusion, these transgenic mice are a novel model of fatal arrhythmia, and are useful model for analysis of endoplasmic reticulum protein such as calreticulin in cardiogenesis.

Report

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

    (6 results)

All 2006 2004

All Journal Article (6 results)

  • [Journal Article] Gene expression profiles of homogentisate-treated Fah-/- Hpd-/-mice using DNA microarrays.2006

    • Author(s)
      Tanaka, Nakamura et al.
    • Journal Title

      Molecular Genetics and Metabolism in press

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Calreticulin negatively regulates the cell surface expression of CFTR2006

    • Author(s)
      Harada, Nakamura et al.
    • Journal Title

      J Biol Chem. e-pub Mar.9

      Pages: 1-11

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Flow-Cytometric Isolation of Endodermal Progenitors from Mouse Salivary Gland Differentiate into Hepatic and Pancreatic Lineages2004

    • Author(s)
      Hisatomi, Nakamura et al.
    • Journal Title

      Hepatology 39

      Pages: 667-675

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary 2004 Annual Research Report
  • [Journal Article] Transient hypothyroidism or Persistent hyperthyrotropinemia in neonates born to mothers with excessive iodate intake.2004

    • Author(s)
      Nishiyama, Nakamura et al.
    • Journal Title

      Thyroid 14

      Pages: 1077-1083

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary 2004 Annual Research Report
  • [Journal Article] Flow-Cytometric Isolation of Endodermal Progenitors from Mouse Salivary Gland Differentiate into Hepatic and Pancreatic Lineages2004

    • Author(s)
      Hisatomi Y, Okumura K, Nakamura K, Matsumoto S, Satoh A, Nagano K, Yamamoto T, Endo F
    • Journal Title

      Hepatology 39

      Pages: 667-675

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Transient hypothyroidism or Persistent hyperthyrotropinemia in neonates born to mothers with excessive iodate intake.2004

    • Author(s)
      Nishiyama S, Mikeda T, Okada T, Nakamura K, Kotani T, Hishinuma A
    • Journal Title

      Thyroid 14

      Pages: 1077-1083

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary

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

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