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Development of Mutant Rats Useful for Analysis of Immediate Hypersensitivity

Research Project

Project/Area Number 03558010
Research Category

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

Allocation TypeSingle-year Grants
Research Field Laboratory animal science
Research InstitutionOsaka University

Principal Investigator

KITAMURA Yukihiko  Osaka Univ Med Sch Professor, 医学部, 教授 (70028520)

Co-Investigator(Kenkyū-buntansha) KONDO Kyoji  Yagi Memorial Park Inst Director, 実験動物研究所, 所長 (60023363)
MATSUDA Hiroshi  Univ Osaka Prefecture Instructor, 農学部, 助手 (80145820)
NISHIMURA Masahiko  Hamamatsu Med Univ Assoc.Prof., 助教授 (20073661)
KASUGAI Tsutomu  Osaka Univ Med Sch Instructor, 医学部, 助手 (80214310)
Project Period (FY) 1991 – 1993
Project Status Completed (Fiscal Year 1993)
Budget Amount *help
¥16,600,000 (Direct Cost: ¥16,600,000)
Fiscal Year 1993: ¥4,600,000 (Direct Cost: ¥4,600,000)
Fiscal Year 1992: ¥4,900,000 (Direct Cost: ¥4,900,000)
Fiscal Year 1991: ¥7,100,000 (Direct Cost: ¥7,100,000)
KeywordsMast Cell / Basophil / c-kit receptor / IgE receptor / Allergy / Mast Cell-Deficient Rat / Intestinal Parasite / 即時型アレルギー / ベージュラット / c-kitレセプター / stem cell factor / 突然変異ラット / 即時型アレルギ- / c-kit遺伝子 / レセプタ-・タイロシンカイネ-ス
Research Abstract

For development of immediate hypersensitivity reaction, IgE and mast cells/basophils are essential. The purpose of the present project is to develop rat models that are useful for the analysis of the immediate hepersensitivity reaction. The following results were obtained. 1).We found that Ws/Ws mutant rats lacked mast cells. The Ws locus of rats encodes the c-kit receptor tyrosine kinase, and the mutant Ws allele is a deletion of 12 bases at the tyrosine kinase domain. The kinase activity of the c-kit was remarkably impaired by this mutation. Although the Ws mutant allele was first found in the BN strain, homozygotes died in utero in this genetic background. In contrast to the BN strain, some homozygotes were obtained when the Ws mutant allele was introduced into DA strain. Now we are attempting to obtain DA-Ws/Ws rats in the specific pathogen-free condition in the colaboration with Japan SLC Co., Ltd. 2).When Ws/Ws rats were infected with Nippostrongylus brasiliensis (NB), connective tissue-type mast cells did not appear, a small number of mucosal mast sells developed and a 50-fold increase of basophils was observed. Therefore, NB-infected normal (+/+) rats may be considered to be mast cells (+) basophils (+) ; NB-infected Ws/Ws rats to be mast cells (-) basophils (+) ; intact +/+ rats to be mast cells (+) basophils (-) ; intact Ws/Ws rats to be mast cells (-) basophils (-). 3).DA-bg/bg rats which had been found by one of us were demonstrated to be useful for studying functions of mast cells.

Report

(4 results)
  • 1993 Annual Research Report   Final Research Report Summary
  • 1992 Annual Research Report
  • 1991 Annual Research Report
  • Research Products

    (40 results)

All Other

All Publications (40 results)

  • [Publications] Niwa,Yoshiki: "Anemia and mast cell depletion in mutant rats that are and mast cell depletion in mutant rats that are homo-zygous at “White spotting (Ws) locus." Blood. 78. 1936-1941 (1991)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] Tsujimura,Tohru: "Characterization of Ws mutant allele of rats : a 12 base deletion in tyrosine kinase domain of c-kit gene." Blood. 78. 1942-1946 (1991)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] Onoue, Hitoshi: "Absence of immature mast cells in the skin of Ws/Ws rats with a small deletion at tyrosine kinase domain of the c-kit gene." American Journal of Pathology. 142. 1001-1007 (1993)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] Kasugai, Tsutomu: "Infection of Nippostrongylus brasiliensis induced normal increase of basophils in mast cell-deficient Ws/Ws rats with a small deletion at the c-kit." Blood. 81. 2521-2529 (1993)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] Arizono,Naoki: "Infection of Nippostrongylus brasilinsis induces development of mucosal-type mast cells in genetically mast cell-deficient Ws/Ws rats." Blood. 81. 2572-2578 (1993)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] Morimoto,Masahiro: "Age-dependent amelioration of hypoplastic anemia in Ws/Ws rats with a small deletion at the kinase domian of c-kit." Blood. 82. 3315-3320 (1993)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] Kitamura,Yukihiko: "Immunopharmacology of Mast Cells and Basophils" Academic Press, 232 (1993)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] Kitamura,Yukihiko: "Biological and Molecular Aspects of Mast Cell and Basophil Differentiation and Function" Raven Press (in press),

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] Niwa, Yoshiki: "Anemia and mast cell depletion in mutant rats that are homozygous at "White spotting (Ws) locus." Blood. 78. 1936-1941 (1991)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] Tsujimura, Tohru: "Characterization of Ws mutant allele of rats : a 12 base deletion in tyrosine kinase domain of c-kit gene." Blood. 78. 1942-1946 (1991)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] Onoue, Hitoshi: "Absence of immature mast cells in the skin of Ws/Ws rats with a small deletion at tyrosine kinse domain of the c-kit gene." American Journal of Pathology. 142. 1001-1007 (1993)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] Kasugai, Tsutomu: "Infection of Nippostrongylus brasiliensis induced normal increase of basophils in mast cell-deficient Ws/Ws rats with a small deletion at the c-kit." Blood. 81. 2521-2529 (1993)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] Arizono, Naoki: "Infection of Nippostrongylus brasiliensis induces development of mucosal-type mast cells in genetically mast cell-deficient Ws/Ws rats." Blood. 81. 2572-2578 (1993)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] Morimoto, Masahiro: "Age-dependent amelioration of hypoplastic anemia in Ws/Ws rats with a small deletion at the kinase domain of c-kit." Blood. 82. 3315-3320 (1993)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] Kitamura, Yukihiko: Immunology of Mast Cells and Basophils.Academic Press, 232 (1993)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] Kitamura, Yukihiko: Biological and Molecular Aspects of Mast Cell and Basophil Differentiation and Function.Raven Press (in press),

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] Onoue,Hitoshi: "Absence of immature mast cells in the skin of Ws/Ws rats with a small deletion at tyrosine kinase domain of the c-kit gene" American Journal of Pathology. 142. 1001-1007 (1993)

    • Related Report
      1993 Annual Research Report
  • [Publications] Kasugai,Tsutomu: "Infection of N.brasiliensis induced normal increase of basophils in mast cell-deficient Ws/Ws rats" Blood. 81. 2521-2529 (1993)

    • Related Report
      1993 Annual Research Report
  • [Publications] Arizono,Naoki: "Infection of N.brasiliensis induces development of mucosal-type but not connective tissue-type mast cells in Ws/Ws rats" Blood. 81. 2572-2578 (1993)

    • Related Report
      1993 Annual Research Report
  • [Publications] Morimoto,Masahiro: "Age-dependent amelioration of hypoplastic anemia in Ws/Ws rats with a small deletion at the kinase domain of c-kit" Blood. 82. 3315-3320 (1993)

    • Related Report
      1993 Annual Research Report
  • [Publications] Tei,Hideki: "Characterization of mast cells derived from Ws/Ws mast cell deficient rats with a small deletion at kinase domain of c-kit" Blood. 83. 916-925 (1994)

    • Related Report
      1993 Annual Research Report
  • [Publications] Kitamura,Yukihiko: "Development of mast cells and basophils:processes and regulation mechanisms" American Journal of Medical Sciences. 306. 185-191 (1993)

    • Related Report
      1993 Annual Research Report
  • [Publications] Kitamura,Yukihiko: "Immunopharmacology of Mast Cells and Basophils" Academic Press,London, 232 (1993)

    • Related Report
      1993 Annual Research Report
  • [Publications] Kitamura,Yukihiko: "Biology of Germ Lines in Animals and Man" Japan Scientific Societies Press, 304 (1993)

    • Related Report
      1993 Annual Research Report
  • [Publications] Kitamura,Yukihiko: "Development of mast cells and basophils:processes and ragulation mechanisms." American Journal of Medical Sciences.

    • Related Report
      1992 Annual Research Report
  • [Publications] Onoue,Hitoshi: "Absence of immature mast cells in the skin if Ws/Ws rats with a small deletion at tyrosine kinase domain of the c-kit gene." American Journal of Pathology.

    • Related Report
      1992 Annual Research Report
  • [Publications] Kasugai,Tsutomu: "Infection of Nippostrongylus brasiliensis induced normal increase of basophils in mast cell-deficient Ws/Ws rats with a small deletion at the kinase domain of c-kit." Blood.

    • Related Report
      1992 Annual Research Report
  • [Publications] Arizono Naoki: "Infection of Nippostrongylus brasiliensis induces development of mucosal-type but not connective tissue-type mast cells in genetically mast cell-deficeint Ws/Ws rats." Blood.

    • Related Report
      1992 Annual Research Report
  • [Publications] Ebi,Yoshitaka: "Low c-kit expression of cultured mast cells of mi/mi genotype may be involved in their defective responses to fibroblasts that express the ligand for c-kit" Blood. 80. 1454-1462 (1992)

    • Related Report
      1992 Annual Research Report
  • [Publications] Jippo-Kanemoto,Tomoko: "BALB/3T3 firbroblast conditioned medium attracts cultured mast cells derived from W/W but not from mi/mi mutant mice,both of which are deficient in mas cells." Blood. 80. 1933-1936 (1992)

    • Related Report
      1992 Annual Research Report
  • [Publications] Kitamura,Yukihiko: "Progress in Allergy and Clinical Immunology" Hogrete & Huber Publishers,Tronto,

    • Related Report
      1992 Annual Research Report
  • [Publications] Kitamura,Yukihiko: "Immunopharmacology of Mast Cells and Basophils" Academic Press,London,

    • Related Report
      1992 Annual Research Report
  • [Publications] Niwa,Yoshiki: "Anemia and mast cell depletion in mutant rats that are homozygous at “White spotting (Ws)"locus." Blood. 78. 1936-1941 (1991)

    • Related Report
      1991 Annual Research Report
  • [Publications] Tsujimura,Tohru: "Characterization of Ws mutant allele of rats:a 12 base deletion in tyrosine kinase domain of c-kit gene." Blood. 78. 1942-1946 (1991)

    • Related Report
      1991 Annual Research Report
  • [Publications] Kitamura,Yukihiko: "Fibroblast-dependent differentiation/proliferation of mast cells" Skin Pharmacology. 4(suppl). 2-7 (1991)

    • Related Report
      1991 Annual Research Report
  • [Publications] Kitamura,Yukihiko: "Usefulness of mast cell-deficient animals for allergy research." Allergy and Clinical Immunology News. 3. 150-153 (1991)

    • Related Report
      1991 Annual Research Report
  • [Publications] Matsuda,Hiroshi: "Nerve growth factor induces development of connective tissue-type mast cells in vitro from murine bone marrow cells." Journal of Experimenal Medicine. 174. 7-14 (1991)

    • Related Report
      1991 Annual Research Report
  • [Publications] Kanemoto,Tomoko: "Effects of culture matrix on differentiation of murine mast cells." Experimental Hematology. 19. 288-293 (1991)

    • Related Report
      1991 Annual Research Report
  • [Publications] Kasugai,Tsutomu: "Proceedings of International Congress on Genetic Intervention in Diseases with Unkown Etiology" Elsevier,Amsterdam,

    • Related Report
      1991 Annual Research Report
  • [Publications] Kitamura,Yukihiko: "Immunopharmacology of Mast Cells and Basophils" Academic Press,London,

    • Related Report
      1991 Annual Research Report

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Published: 1991-04-01   Modified: 2016-04-21  

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