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Gene targeting of natriuretic peptide family and their functional analyzes

Research Project

Project/Area Number 05680569
Research Category

Grant-in-Aid for General Scientific Research (C)

Allocation TypeSingle-year Grants
Research Field Functional biochemistry
Research InstitutionNational Cardiovascular Center Research Institute

Principal Investigator

MINAMINO Naoto  National Cardiovascular Center Research Institute, Pharmacology, Head, 薬理部, 室長 (50124839)

Co-Investigator(Kenkyū-buntansha) MIYAMOTO Kaoru  National Cardiovascular Center Research Institute, Bioscience, Head, バイオサイエンス部, 室長 (30125877)
MATSUO Hisayuki  National Cardiovascular Center Research Institute, Director General, 所長 (50028685)
Project Period (FY) 1993 – 1994
Project Status Completed (Fiscal Year 1994)
Budget Amount *help
¥2,000,000 (Direct Cost: ¥2,000,000)
Fiscal Year 1994: ¥900,000 (Direct Cost: ¥900,000)
Fiscal Year 1993: ¥1,100,000 (Direct Cost: ¥1,100,000)
KeywordsNatriuretic peptide / Gene targeting / Natriuretic peptide receptor / Gene structure analysis / Blood pressure regulation / Growth and differentiation / Molecular Biology / 機能解析 / 遺伝子構造 / マウス
Research Abstract

Natriuretic peptide family is comprised of three peptides (ANP,BNP,CNP). These peptides bind receptor quanylate cyclase (GC-A and GC-B), increase cGMP concentration, and alter cell functions. ANP and BNP mainly function as cardiac hormones regulating blood pressure, while CNP is a neuropeptide in brain or a local regulator in the vascular wall. In order to elucidate their in vivo functions and estimate the contribution to blood pressure regulation, we have planned to establish a mouse which is deleted the natriuretic peptide genes by using the newly developed gene targeting method.
We cloned mouse ANP,BNP and CNP gene of 5-6 kb containing complete sets of each exons. About 3-6 kb sequence of each gene was determine. In the case of CNP gene, the third exon region was first sequenced by the present study. In addition to three natriuretic peptide genes, we further cloned mouse GC-A and GC-B gene to analyze their functions. Portions of GC-A and GC-B gene structure containing functional domains are now being determined. By a series of these studies, appropriate fragments used for the gene targeting of the natriuretic peptides and their receptors have been obtained, and most of the sequences have already determined.

Report

(3 results)
  • 1994 Annual Research Report   Final Research Report Summary
  • 1993 Annual Research Report
  • Research Products

    (26 results)

All Other

All Publications (26 results)

  • [Publications] M.Kojima et al.: "Cloning and characterization of a novel natriuretic peptide in frog (Rana catesbeiana)." J.Biol.Chem.269. 13136-13140 (1994)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Y.Ishizaka et al.: "Adrenomedullin stimulates cyclic AMP formation in rat vascular smooth muscle cells." Biochem.Biophys.Res.Commun.200. 642-646 (1994)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] S.Sugo et al.: "Endothelial cells actively synthesize and secrete adrenomedullin." Biochem.Biophys.Res Commun.201. 1160-1166 (1994)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] T.Nishikimi et al.: "Role of endogenous atrial natriuretic peptide on systemic and renal hemodynamics in heart failure rats:Endogenous ANP in geart failure." Am.J.Physiol.267. H182-H196 (1994)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] K.Kitamura et al.: "Identification and hypotensive activity of proadrenomedullin N-terminal 20 peptide(PAMP)." FEBS Lett.351. 35-37 (1994)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] S.Sugo et al.: "Production and secretion of adrenomedullin from vascular smooth muscle cells:Augmented production by tumor necrosis factor-α" Biochem.Biophys.Res.Commun.203. 719-726 (1994)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] E.Suzuki, et al.: "Evidence for C-type natriuretic peptide production in the rat kidney." Biochem.Biophys.Res.Commun.192. 532-538 (1993)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] M.Furuya, et al.: "C-type natriuretic peptide inhibits intimal thickenting after vascular injury." Biochem.Biophys.Res.Commun.193. 248-253 (1993)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] N.Yokota, et al.: "Alteration in circulating and cardiac tissue concentrations of brain natriuretic peptide in spontaneously hypertensive rats." Cardiovascul.Res.27. 1312-1315 (1993)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] N.Minamino, et al.: "Distribution of C-type natriuretic peptide and its messenger RNA in rat central nervous system and peripheral tissue." Biochem.Biophys.Res.Commun.197. 326-335 (1993)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] K.Kangawa, et al.: "Four novel tachykinins in frog (Rana catesbeiana) brain and intestine." Regul.Pept.46. 81-88 (1993)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Y.Ishizaka, et al.: "Plasma concentration of human brain natriuretic peptide in patients on hemodialysis." Am.J.Kid.Dis.24. 461-472 (1994)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] M.Kojima, et al.: "Cloning and characterization of a novel natriuretic peptide in frog (Rana catesbeiana)." J.Biol.Chem.269., 18. 13136-13140 (1994)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Y.Ishizaka, et al.: "Adrenomedullin stimulates cyclic AMP formation in rat vascular smooth muscle cells." Biochem.Biophys.Res.Commun.200. 642-646 (1994)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] S.Sugo, et al.: "Endothelial cells actively synthesize and secrete adrenomedullin." Biochem.Biophys.Res.Commun.201. 1160-1166 (1994)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Y.Hirata, et al.: "Mechanisms underlying the augmented responses of deoxycorticosterone acetate-salt hypertensive rats to neutral endopeptidase inhibitors." J.Hypertens.12. 367-374 (1994)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] T.Nishikimi, et al.: "Role of endoenous atrial natriuretic peptide on systemic and renal hemodynamics in heart failure rats : Endogenous ANP in heart failure." Am.J.Physiol.267. H182-186 (1994)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] K.Kitamura, et al.: "Identification and hypotensive activity of proadrenomedullin N-terminal 20 peptide (PAMP)." FEBS Lett.351. 35-37 (1994)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] S.Sugo, et al.: "Production and secretion of adrenomedullin from vascular smooth muscle cells : Augmented production by tumor necrosis factor-alpha." Biochem.Biophys.Res.Commun.203. 719-726 (1994)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] S.Sugo, et al.: "Interleukin-1, tumor necrosis factor and lipopolysaccharide additively stimulate production of adrenomedullin in vascular smooth muscle cells." Biochem.Biophys.Res.Commun.207. 25-32 (1995)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] M.Kojima,et al.: "Cloning and characterization of a novel natriuretic peptide in frog (Rana catesheiana.)" J.Biol.Chem.269. 13136-13140 (1994)

    • Related Report
      1994 Annual Research Report
  • [Publications] Y.Ishizaka,et al.: "Adrenomedullin stimulates cyclic AMP formation in rat vascular smooth muscle cells." Biochem.Biophys.Res.Commun.200. 642-646 (1994)

    • Related Report
      1994 Annual Research Report
  • [Publications] S.Sugo,et al.: "Endothelial cells actively synthesize and secrete adrenomedullin." Biochem.Biophys.Res.Commun.201. 116-1166 (1994)

    • Related Report
      1994 Annual Research Report
  • [Publications] T.Nishikimi,et al.: "Role of endogenous strial natriuretic peptide on systemic and renal hemodynamics in heart failure rats;Endogenous ANP in heart failu" Am.J.Physiol.267. H182-H186 (1994)

    • Related Report
      1994 Annual Research Report
  • [Publications] K.Kitamura,et al.: "Identification and hypotensive activity of proadrenomedullin N-terminal 20 peptide (PAMP)." FEBS Lett.351. 35-37 (1994)

    • Related Report
      1994 Annual Research Report
  • [Publications] S.Sugo,et al.: "Production and secretion of adrenomedullin from vascular smooth muscle cells:Augmented production by tumor necrosis factor-α." Biochem.Biophys.Res.Commun.203. 719-726 (1994)

    • Related Report
      1994 Annual Research Report

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Published: 1993-04-01   Modified: 2016-04-21  

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