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Transgenic mice and knock out mice in renin-angiotensin system.

Research Project

Project/Area Number 06404016
Research Category

Grant-in-Aid for Scientific Research (A)

Allocation TypeSingle-year Grants
Section一般
Research Field Applied molecular and cellular biology
Research InstitutionUNIVERSITY OF TSUKUBA

Principal Investigator

MURAKAMI Kazuo  University of Tsukuba, Institute of Applied Biochemistry, Professor, 応用生物化学系, 教授 (70110517)

Co-Investigator(Kenkyū-buntansha) NOMURA Tatuji  Laboratory Animal Research Center, Director, 所長 (10072399)
SUGIYAMA Fumihiro  University of Tsukuba, Basic Medicine, Assistant Prof., 基礎医学系, 講師 (90226481)
FUKAMIZU Akiyoshi  University of Tsukuba, Institute of Applied Biochemistry, Associate Prof., 応用生物化学系, 助教授 (60199172)
MIYAZAKI Hitoshi  University of Tsukuba, Institute of Applied Biochemistry, Associate Prof., 応用生物化学系, 助教授 (40183636)
Project Period (FY) 1994 – 1996
Project Status Completed (Fiscal Year 1996)
Budget Amount *help
¥29,100,000 (Direct Cost: ¥29,100,000)
Fiscal Year 1996: ¥3,300,000 (Direct Cost: ¥3,300,000)
Fiscal Year 1995: ¥7,000,000 (Direct Cost: ¥7,000,000)
Fiscal Year 1994: ¥18,800,000 (Direct Cost: ¥18,800,000)
Keywordsrenin / angiotensinogen / angiotensin II / angiotensin-receptor / knock out mice / transgenic mice / Hypotensin / Hypertension induced by pregnancy / つくば高血圧マウス / つくば低血圧マウス / アンギオテンシンノーゲン遺伝子 / レニン・アンギオテンシン系 / ジーンターゲテイング法 / アンギオテンシンII受容体欠損マウス / アンギオテンシノーゲン遺伝子 / アンギオテンシンI
Research Abstract

The important research results in this project are summarized in the fololowing two sections.
(1) Angiotensinogen-Deficient Mice with Hypotension
The renin-angiotensin system is an enzymatic cascade that produces a potent vasoconstrictor octapeptide angiotensin II,through its physiologically inactive intermediate decapeptide angiotensin I,from their precursor angiotensinogen. In the present study, we generated angiotensinogen-deficient mice by homologous recombination in mouses embryonic stem cells. These mice do not produce angiotensinogen in the liver, resulting in the complete loss of plasma immunoreactive angiotensin I.The systolic blood pressure of the homozygous mutant mice was 66.9 <plus-minus> 4.1 mmHg, significantly lower than that of wild-type mice (100.4 <plus-minus> 44 mmHg). This profound hypotension in angiotensinogen-deficient mice demonstrates an indispensable role for the renin-angiotensin system in maintaining blood press
(2) Hypertension Induced in Pregnant Mice by Placental Renin and Maternal Angiotensinogen
Maternal hypertension is a common complication of pregnancy and its pathophysiology is poorly understood. This phenomenon was studied in an animal model by mating transgenic mice expressing components of the human renin-angiotensin system. When transgenic females expressing angiotensinogen were mated with transgenic males expressing renin, the pregnant females displayd a transient elevation of blood pressure in late pregnancy, due to secretion of placental human renin into the maternal circulation. Blood pressure returned to normal levels after delivery of the pups. Histopathologic examination revealed uniform enlargement of glomeruli associated with an increase in urinary protein excretion, myocardial hypertrophy, and necrosis and edema in the placenta. These mice may provide molecular insights into pregnancy-associated hypertension in humans.

Report

(4 results)
  • 1996 Annual Research Report   Final Research Report Summary
  • 1995 Annual Research Report
  • 1994 Annual Research Report
  • Research Products

    (40 results)

All Other

All Publications (40 results)

  • [Publications] Y.Nibu et al.: "Identification of cell type-dependent enhancer core element located in the 3'-downstream region of the human angiotensinogen gene." J.Biol.Chem.269. 28598-28605 (1994)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] A.Fukamizu et al.: "Neuroectodermal tumors expressing c-,L-,and N-myc in transgenic mice that carry the E1A/E1B gene of human adenovirus type 12." J.Biol.Chem.269. 31252-31258 (1994)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] K.Tanimoto et al.: "Angiotensinogen-deficient mice with hypotension." J.Biol.Chem.269. 31334-31337 (1994)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] M.Sagara et al.: "Activation of the nuclear oncogenes N-myc and c-jun in cartinoid tumors of transgenic mice carrying the human adenovirus type 12E1 region gene." DNA and Cell Biology. 14. 95-101 (1995)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] F.Sugiyama et al.: "Heritable formation of neuroectodermal tumor in transgenic mice carrying the combined E1 region gene of adenovirus type 12 with the deregulated human renin promoter." J.Cellular Biochemistry. 57. 691-700 (1995)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] S.Shimada et al.: "Identification of two distiact Spl and RBF-l-like nuclear factors that bind to the upstream region of the humanangiotensl nogen promot" Endocrine. 3. 543-547 (1995)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] K.Tamura et al.: "Recent advances in the studuy of renin and angiotensinogen genes : from molecules to the whole body." Hypertension Res.18. 7-18 (1995)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] A.Fukamizu et al.: "New aspects of the renin-angiotensin system in blood pressure regulation." Trends Endocrinol Metab.6. 279-284 (1995)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] R.Morishita et al.: "Role of transcriptional cis-elements,angiotensinogen gene-activating elements,of angiotensinogen gene in blood pressure regulation." Hypertension. 27. 502-507 (1996)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] K.Tamura et al.: "Tissue-specific regulation of angiotensinogen gene expression in spontaneously hypertensive rats." Hypertension. 27. 1216-1223 (1996)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] K.Yanai et al.: "A cis-acting DNA element located between TATA box and transcription initiation site is critical in response to regulatory sequences in human angiotensinogen gene." J.Biol.Chem.271. 15981-15986 (1996)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] K.Murakami et al.: "Hypertensive and hypotensive mice produced by the introduction and disruption of genes on the renin-angiotensin system." Blood Pressure. 5. 36-40 (1996)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] E.Takimoto et al.: "Hypertension induced in pregnant mice by placental renin and maternal angiotensinogen." Science. 274. 995-998 (1996)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Y.Watanabe et al.: "Chromosomal mapping of human angiotensinogen gene and human renin gene by fluorescence in situ hybridization (FISH) in transgenic mice" Exp.Anim.,. 45. 265-269 (1996)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Y.Nibu et al.: "Identification of cell type-dependent enhancer core element located in the 3'-downstream region of the human angiotensinogen gene." J.Biol.Chem.269. 28598-28605 (1994)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] A.Fukamizu et al.: "Neuroectodermal tumors expressing c-, L-, and N-myc in transgenic mice that carry the E1A/E1B gene of human adenovirus type 12." J.Biol.Chem.269. 31252-31258 (1994)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] K.Tanimoto et al.: "Angiotensinogen-deficient mice with hypotension." J.Biol.Chem.269. 31334-31337 (1994)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] M.Sagara et al.: "Activation of the nuclear oncogenes N-myc and c-jun in cartinoid tumors of transgenic mice carrying the human adenovirus type 12E1 region gene." DNA and Cell Biology. 14. 95-101 (1995)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] F.Sugiyama et al.: "Heritable formation of neuroectodermal tumor in transgenic mice carrying the combined E1 region gene of adenovirus type 12 with the deregulated human renin promoter." J.Cellular Biochemistry. 57. 691-700 (1995)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] S.Shimada et al.: "Identification of two distinct Sp1-and RBF-1-like nuclear factors that bind to the upstream region of the human angiotensinogen promoter." Endocrine. 3. 543-547 (1995)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] K.Tamura et al.: "Recent advances in the study of renin and angiotensinogen genes : from molecules to the whole body." Hypertension Res.18. 7-18 (1995)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] A.Fukamizu et al.: "New aspects of the renin-angiotensin system in blood pressure regulation." Trends Endocrinol Metab.6. 279-284 (1995)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] K.Yanai et al.: "A cis-acting DNA element located between TATA box and transcription initiation site is critical in response to regulatory sequences in human angiotensinogen gene." J.Biol.Chem.271. 15981-15986 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] R.Morishita et al.: "Role of transcriptional cis-elements, angiotensinogen gene-activating elements, of angiotensinogen gene in blood pressure regulation." Hypertension. 27. 502-507 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] K.Tamura et al.: "Tissue-specific regulation of angiotensinogen gene expression in spontaneously hypertensive rats." Hypertension. 27. 1216-1223 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] K.Murakami et al.: "Hypertensive and hypotensive mice produced by the introduction and disruption of genes on the renin-angiotensin system." Blood Pressure. 5. 36-40 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Y.Watanabe et al.: "Chromosomal mapping of human angiotensinogen gene and human renin gene by fluorescence in situ hybridization (FISH) in transgenic mice." Exp.Anim.45. 265-269 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] E.Takimoto et al.: "Hypertension induced in pregnant mice by placental renin and maternal angiotensinogen." Science. 274. 995-998 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] R.Morishita et al.: "Role of transcriptional cis-elements,angiotensinogen gene-activatiing elements,of angiotensinogen gene in blood pressure regulation." Hypertension. 27. 502-507 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] K.Tamura et al.: "Tissue-specific regulation of angiotensinogen gene experssion in spontaneously hypertensive rats." Hypertension. 27. 1216-1223 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] K.Yanai et al.: "A cis-acting DNA element located between TATA box and transcription initiation site is critical in response to regulatory sequences in human angiotensinogen gene." J.Biol.Chem.271. 15981-15986 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] K.Murakami et al.: "Hypertensive and hypotensive mice produced by the introduction and disruption of genes on the renin-angiotensin system." Blood Pressure. 5. 36-40 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] M.Tanaka et al.: "Characterization of angiotensin II receptor type 2 during differentiation and apoptosis of rat ovarian cultured granulosa cells." Biochem. Biophys. Res. Commun.207. 593-598 (1995)

    • Related Report
      1995 Annual Research Report
  • [Publications] S.Kobayashi et al.: "Cloning of the rat angiotensin II type 2 receptor gene and identification of its functional promoter region." Biochimica et Biophysica Acta. 1262. 155-158 (1995)

    • Related Report
      1995 Annual Research Report
  • [Publications] N.Fujii et al.: "Alterations of angiotensin II receptor contents in hypertrophied hearts." Biochem. Biophys.Res.Commun.212. 326-333 (1995)

    • Related Report
      1995 Annual Research Report
  • [Publications] T. Sugaya et al.: "Angiotensin II type la receptor-deficient mice with hypotension and hyperreninemia." J. Biol. Chem.270. 18719-18722 (1995)

    • Related Report
      1995 Annual Research Report
  • [Publications] K.Tanimoto et al.: "Angiotensinogen-deficient mice with hypotension." J.Biol.Chem.269. 31334-31337 (1994)

    • Related Report
      1994 Annual Research Report
  • [Publications] U.Nibu et al.: "A cell type-dependent enhancer core element is located in exon 5 of the human angiotensinogen gene." Biochem.Biophys.Res.Commun.205. 1102-1108 (1994)

    • Related Report
      1994 Annual Research Report
  • [Publications] A.Fukamizu et al.: "Cortical expression of the human angiotensinpogen gene in the kidney of transgonic mice." Kidney International. 46. 1533-1535 (1994)

    • Related Report
      1994 Annual Research Report
  • [Publications] K.Tamura et al.: "Mechanism of cAMP regulation of renin gene transcription by proximal promoter." J.Clin.Invest.94. 1959-1967 (1994)

    • Related Report
      1994 Annual Research Report

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Published: 1994-04-01   Modified: 2016-04-21  

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