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2000 Fiscal Year Final Research Report Summary

Development of practically usefull Ws/Ws rat and its utilization

Research Project

Project/Area Number 10558121
Research Category

Grant-in-Aid for Scientific Research (B).

Allocation TypeSingle-year Grants
Section展開研究
Research Field Laboratory animal science
Research InstitutionOsaka University

Principal Investigator

HIROTA Seiichi  Osaka Univ.Grad.Sch.Med.Associate professor, 医学系研究科, 助教授 (50218856)

Co-Investigator(Kenkyū-buntansha) ASAI Hidekazu  Japan SLC Co.Ltd.Head of Haruno Branch, 春野支店長(研究職)
MORII Eiichi  Osaka Univ.Grad.Sch.Med.Assistant professor, 医学系研究科, 助手 (10283772)
JIPPO Tomoko  Osaka Univ.Grad.Sch.Med.Assistant professor, 医学系研究科, 助手 (70252658)
Project Period (FY) 1998 – 2000
Keywordsc-kit gene / mutant rats / Ws / Ws / intrapyloric pressure / fibrosis / memory
Research Abstract

Ws/Ws rat is only the mutant of rat c-kit gene that we first found in the world in 1991. The c-kit gene encodes a receptor tyrosine kinase, KIT.And the ligand for KIT is stem cell factor, SCF.The KIT-SCF system is essential for development of mast cells and interstitial cell of Cajal(ICC). At present, brothers and sisters of rats that have Ws mutation are crossed each other through several generations in SLC Japan Co.Ltd.Ws/Ws rats will be stably available in near future.
We carried out several investigations using Ws/Ws rats. First, the function of pyloric ring was examined by measuring intrapyloric pressure. In ICC-deficient Ws/Ws rats, the contraction pressure did not prolong as observed in +/+ rats, and spike-like waves were noted. The abnormal spike-like waves were considered to be a cause of bile reflux into stomach observed in Ws/Ws rats. Second, the role of mast cells in fibrosis was examined using mast cell-deficient Ws/Ws rats. In both lung and liver fibrosis models, fibrosis in Ws/Ws rats was more prominent than that in +/+ rats, suggesting that the increase of mast cells in fibrotic tissues is not a cause but a result of fibrosis. Third, we examined the role of KIT receptor in central nervous system by using Ws/Ws rats. Morris maze task revealed the impairment of spatial learning and the electrophysiological examination of hippocampal slice showed the impairment of synaptic potentiation in Ws/Ws rats.

  • Research Products

    (15 results)

All Other

All Publications (15 results)

  • [Publications] Nakama A: "Disturbed pyloric motility in Ws/Ws mutant rats due to deficiency of c-kit-expressing interstitial cells of cajal"Pathol Int. 48. 843-849 (1998)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Hirota S: "Gain-of-function mutations of c-kit in human gastrointestinal stromal tumors."Science. 279. 577-580 (1998)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Okazaki T: "Increase of mast cells in the liver and lung may be associated with but not a cause of fibrosis : demonstration using mast cell-deficient Ws/Ws rats"Lab Invest. 78. 1431-1438 (1998)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Nishida T: "Familial gastrointestinal stromal tumors with gesmline mutation of KIT"Nature Genet. 19. 323-324 (1998)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Katafuchi T: "Impairment of spatial learning and hippocampal synaptic potentiation in c-kit mutant rats"Learn Mem. 7. 383-392 (2000)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Hirota S: "Gain-of-function mutation at extra cellular domain of KIT in gastrointestinal stromal tumors"J Pathol. (in press).

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Nakama A, et al: "Disturbed pyloric motility in Ws/Ws mutant rats due to deficiency of c-kit-expressing intersititial cells of Cajal."Pathol Int.. 48. 843-849 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Okazaki T, et al: "Increase of mast cells in the liver and lung may be associated with but not a cause of fibrosis : demonstration using mast cell-deficient Ws/Ws rats."Lab Invest.. 78. 1431-1438 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Hirota S, et al: "Gain-of-function mutations of c-kit in human gastrointestinal stromal tumors."Science.. 279. 577-580 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Nishida T, et al: "Familial gastrointestinal stromal tumors with germ line mutation of KIT."Nature Genet.. 19. 323-324 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Taniguchi M, et al: "Effect of c-kit mutation on prognosis of gastrointestinal stromal tumors."Cancer Res.. 59. 4297-4300 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Hirota S, et al: "Cause of familial and multiple gastrointestinal autonomic nerve tumors with hyperplasia of interstitial cells of Cajal is germline mutation of the c-kit gene."Am J Surg Pathol.. 24. 326-327 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Katafuchi T, et al: "Impairment of spatial learning and hippocampal synaptic potentiation in c-kit mutant rats."Learn Mem.. 7. 383-392 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Isozaki K, et al: "Germ-line activating mutation in the kinase domain of c-kit gene in familial gastrointestinal stromal tumors."Am J Pathol.. 157. 1581-1585 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Hirota S, et al: "Gain-of-function mutation at extracellular domain of KIT in gastrointestinal stromal tumors."J Pathol.. (In press.).

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

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Published: 2002-03-26  

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