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1997 Fiscal Year Final Research Report Summary

Novel methods to avoid difficulties from juvenile lethality or growth retardation in knockout mice and to study circulatory, respiratory, and autonomic functions in them

Research Project

Project/Area Number 08457008
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field General physiology
Research InstitutionChiba University (1997)
The University of Tokyo (1996)

Principal Investigator

KUWAKI Tomoyuki  Chiba University, Department of Physiology, Lecturer, 医学部, 講師 (80205260)

Co-Investigator(Kenkyū-buntansha) YOKOMORI Kinji  Japan Red Cross Medical Center, Department of Pediatric Surgery, Department Head, 小児外科, 部長 (20251291)
KURIHARA Hiroki  University of Tokyo, Department of Internal medicine, Assistant, 医学部付属病院, 助手 (20221947)
Project Period (FY) 1996 – 1997
Keywordsknockout mouse / endothelin-1 / endothelin A receptor / endothelin B receptor / arterial blood pressure / insulin receptor / respiratory reflex / central chemosensitivity
Research Abstract

Five methods were developed to avoid difficulties from juvenile lethality or growth retardation in knockout mice and to study circulatory, respiratory, and autonomic functions in them : to make medulla-spinal cord preparation from newborn mice, a way to rescue newborn pups with tracheotomy, special small devices to measure blood pressure and respiratory mechanics, construction of artificial anus, and genetic rescue. These methods were applied to endothelin (ET) -1 knockout mouse, ET-A receptor (ETAR) knockout mouse, ET-B receptor (ETBR) knockout mouse, and insulin receptor substrate-1 (IRS-1) knockout mouse. Medulla-spinal cord preparation from ET-1 knockout mice and tracheotomized newborn mice of ET-1 knockout and ETAR knockout showed severe attenuation of respiratory reflex to hypercapnia. Endogenous ET-1-ETAR system thus physiologically participates in the central chemosensitivity. In genetically established mutant mice in which ETBR was 1/8 of normal mice, arterial blood pressure (AP) was elevated with normal sympathetic activity and respiration. The result is consistent with a pressor response to selective blockade of ETBR in normal mice. Thus, ETBR contribute physiologically to diminish basal level of AP through peripheral mechanism. IRS-1 knockout mice showed growth retardation and elevation of AP.Thus IRS-1 is also essential to maintain normal AP.In conclusion, knockout mice are a valuable research resource especially in the study of integrative physiological functions of mammals.

  • Research Products

    (27 results)

All Other

All Publications (27 results)

  • [Publications] T.Kuwaki: "Inpaired ventilatory responses to hypoxia andheperopnia in mutant mice deficient in endothelin-1" American Journal of Physiolosy. 270. 279-R1286 (1996)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] T.Kuwaki: "Physiological rde of the endothelin in the untral autonomic control;From neuron to knockout mouse" Progress in Neurobiolosy. 51. 545-579 (1997)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] M.Onodera: "Determination of ventilatory volume in mice by ruhik body plethysmogrephy" Japanese Journal of Pysiolosy. 47. 317-326 (1997)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] D.E.Clouthier: "Cranial and cardiac neural crest defects in endothelin-A receptor-deficient mice" Development. 125. 813-824 (1998)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] H.Abe: "Hypertension,hyperglyceridemia,and impaired endothelium-dependent vascular relaxation in mice lacking insulin receptor substrate-1" Journal of Clinical Investigation. in press (1998)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] K.H.Ju: "Power spectral analysis of heart rate variability in ryanodipe receptor Type-3 knockout mice" Proceedings of 16th Southern Biomedical Engineering Conference. 120-123 (1997)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] T.Kuwaki: "Modulatory impact of stress on the central control of circulation" Cardioangiolosy. 42. 387-391 (1997)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] T.Kuwaki: "Endothelin-B receptor and endothelin-3 knockout mice: Novul model animals for the study of hirschsprung.disease" Japanese Journal of Pediatric Surgery. 29. 217-222 (1997)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] K.H.Ju: "Power spectral analysis of variability of blood pressure and R-Rintervals of the electrocardiograrn Effect of environmental and genetic factors" The Autonomic Nervous System. 34. 214-218 (1997)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] 熊田 衛: "循環中枢の新しい考え方" Clinical Neurosvence. 15(4). 377-379 (1997)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] 熊田 衛: "ノックアウトマウス:循環研究の新しい資源" 心臓. 29. 77-79 (1997)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] O.Y.Ling: "Rend sympathetic nerve activity and its control by baro-and clomo-receptor reflex in endothelin-1deficient mice" Neuroscience Research. suppl.20. S78-S78 (1996)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] W.H.Cao: "Abnormal central respiratory mechanism in endothelin-1 deficient mice:a study in modulla-spinal cord preparation" Newroscience Research. suppl.20. S72-S72 (1996)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] 前村 浩二: "エンドセリン遺伝子過剰発現マウスの樹立と解析" Japanese Circulation Journal. 60(Suppl.I). 339-339 (1996)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] 栗原 由紀子: "エンドセリン-1遺伝子欠損マウスのストレス反応の検討" Japanese Circulation Journal. 61. 324-324 (1997)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] 桑木 共之: "循環研究プロトコール-動脈硬化・高血圧・心臓病研究の最前線" 羊工社(東京), 209 (1996)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] T.Kuwaki, et al.: "Impaired ventilatory responses to hypoxia and hypercapnia in mutant mice deficient in endothelin-1" American Journal of Physiology. 270. R1279-R1286 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] T.Kuwaki, et al.: "Physiological role of brain endothelin in the central autonomic control : from neuron to knockout mouse" Progress in Neurobiology. 51. 545-579 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] M.Onodera, et al.: "Determination of ventilatory volume in mice by whole body plethysmography" Japanese Journal of Physiology. 47. 317-326 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] D.E.Clouthier, et al.: "Crania and cardiac neural crest defects in endothelin-A receptor-deficient mice" Development. 125. 813-824 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] H.Abe, et al.: "Hypertension, hyperglyceridemia, and impaired endothelium-dependent vascular relaxation in mice lacking insulin receptor substrate-1" J Clin Invest. (in press). (1998)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] K.H.Ju, et al.: "Power spectral analysis of heart rate variability in ryanodine receptor type-3 knockout mice" Proceedings of 16th Southern Biomedical Engineering Conference. 120-123 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] T.Kuwaki: "Modulatory impact of stress on the central control of circulation" Cardioangiology. 42. 387-391 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] T.Kuwaki: "Endothelin-B receptor and endothelin-3 knockout mice : Novel model animals for the study of Hirschsprung disease" Japanese Journal of Pediatric Surgery. 29. 217-222 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] K.H.Ju, et al.: "Power spectral analysis of variability of blood pressure and R-R intervals of the electrocardiogram : Effect of environmental and genetic factors" The Autonomic Nervous System. 34. 214-218 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] G.Y.Ling, et al.: "Renal sympathetic nerve activity and its control by baro- and chemo-receptor reflex in endothelin-1 deficient mice" Neuroscience Research. Suppl 20. S78-S78 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] W.H.Cao, et al.: "Abnormal central respiratory mechanism in endothelin-1 deficient mice : a study in medulla-spinal cord preparation" Neuroscience Research. Suppl 20. S72-S72 (1996)

    • Description
      「研究成果報告書概要(欧文)」より

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Published: 1999-03-16  

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