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Research on the function of a single transmembrane metalloprotease of mouse ADAM33

Research Project

Project/Area Number 14580751
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Neurochemistry/Neuropharmacology
Research InstitutionFujita Health University

Principal Investigator

SAWADA Hirohide  Fujita Health University, Institute For Comprehensive Medical Science, assistant, 総合医科学研究所, 助手 (30247663)

Co-Investigator(Kenkyū-buntansha) NISHII Kazuhiro  Fujita Health University, Education and research center of animal models for human diseases, assistant, 疾患モデル教育研究センター, 助手 (50278305)
ISHIGURO Hiroshi  Carna Bioscience Inc., Research head office, Research director, 研究本部, 部長 (20211039)
Project Period (FY) 2002 – 2003
Project Status Completed (Fiscal Year 2003)
Budget Amount *help
¥3,600,000 (Direct Cost: ¥3,600,000)
Fiscal Year 2003: ¥1,700,000 (Direct Cost: ¥1,700,000)
Fiscal Year 2002: ¥1,900,000 (Direct Cost: ¥1,900,000)
KeywordsADAN33 / Metalloprotease / Disintegrin / ADAM13 / Transgenic mouse / ADAM遺伝子 / 膜1貫通型 / 喘息 / 連鎖解析
Research Abstract

A disintegrin and metalloprotease (ADAM) family of the single transmembrane proteins has a unique domain structure, containing metalloprotease, disintegrin and EGF-like domains. 34 ADAMs have been identified to date. 17 ADAMs contain the unique amino acid sequence (HE-X-H-XX-G-XX-HD) in their metalloprotease domain required for enzymatic activity. We isolated novel mouse ADAM33 gene from the cDNA library in mouse brain, which is highly resembled the Xenopus ADAM13, suggesting play a role of the formation of early neural crest and neural tube. We investigated their nucleotide and amino acid sequence. The mouse ADAM33 amino acid sequence showed 42%. homology with Xenopus ADAM13, but both proteins were conserved their functional domains in protein structures. We also isolated the human ADAM33 gene, and this amino acid sequence showed the highest homology with mouse ADAM33 (70%).
To clarify the function of mouse ADAM33, we generated transgenic mice using the DNA fragment containing chloramphenicol acetyltransferase (CAT) gene inserted between exogenous promoter and mouse ADAM33 gene. And then constructed DNA was microinjected into fertilized eggs. The transcriptional effects of this introduction in generated transgenic mice were analyzed with ELISA method, no obvious highly transcriptional mice were obtained. We resume generating the transgenic mice with alterative gene-structure, mouse ADAM33 gene was directly connected with their promoter.

Report

(3 results)
  • 2003 Annual Research Report   Final Research Report Summary
  • 2002 Annual Research Report
  • Research Products

    (26 results)

All Other

All Publications (26 results)

  • [Publications] Tsuyoshi Yoshinaka: "Identification and characterization of novel mouse and human ADAM33s with potential metalloprotease activity"Gene. 282. 227-236 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Masanori Asakura: "Cardiac hypertrophy is inhibited by antagonism of ADAM12 processing of HB-EGF : Metalloproteinase inhibitors as a new therapy"Nature Medicine. 8. 35-40 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Naohiro Ichino: "Increase of transcriptional levels of egr-1 and nur77 genes due to both nicotine treatment and withdrawal in pheochromocytoma cells"J.Neural Transmission. 109. 1015-1022 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Hiroshi Ishiguro: "Dopamine neurons are not affected by expanded polyglutamine stretches in HD gene knock-in mice"Advances in Behavioral Bilogy, Catecholamine Research. 53. 99-102 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Seiji Mori: "PACSIN3 binds ADAM12/meltrin α and up-regulates ectodomain shedding of heparin-binding epidermal growth factor-like growth factor"J.Biological Chemistry. 278. 46029-46034 (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Norihiko Nakano: "The N-terminal region of NTAK/neuregulin-2 isoforms has an inhibitory activity on angiogenesis"J.Biological Chemistry. 279. 11465-11470 (2004)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] 石黒 啓司: "ハンチントン病の動物モデル(神経研究の進歩)"澤田 浩秀、西井 一宏、山田 晃司、永津 俊治. 11(747-757) (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Yoshinaka T., Nishii K., Yamada K., Sawada H., Nishiwaki E., Smith K., Yoshino K, Ishiguro H., Higashiyama S.: "Identification and characterization of novel mouse and human ADAM33s with potential metalloprotease activity."Gene. 282. 227-236 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Asakura M., Kitakaze M., Takashima S., Liao Y., Ishikura F., Yoshinaka T., Ohmoto H., Node K., Yoshino K., Ishiguro H., Asanuma H., Sanada S., Matsumura Y., Takeda H., Beppu S., Tada M., Hori M., Higashiyama S.: "Cardiac hypertrophy is inhibited by antagonism of ADAM12 processing of HB-EGF: Metalloproteinase inhibitors as a new therapy."Nat.Med.. 8. 35-40 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Ichino N., Yamada K, Nishii K., Sawada H., Nagatsu T., Ishiguro H.: "Increase of transcriptional levels of egr-1 and nur77 genes due to both nicotine treatment and withdrawal in pheochromocytoma cells."J.Neural Transm.. 109. 1015-1022 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Ishiguro H., Yamada K, Sawada H., Nishii K., Sawada M., Goto J., Kanazawa I., Nagatsu T.: "Dopamine neurons are not affected by expanded polyglutamine stretches in HD gene knock-in mice."Advances in Behavioral Biology (Catecholamine Research). Vol.53. 99-102 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Mori S., Tanaka M., Nanba D., Nishiwaki E., Ishiguro H., Higashiyama S., Matsuura N.: "PACSIN3 binds ADAM12/meltrin α and up-regulates ectodomain shedding of heparin-binding epidermal growth factor-like growth factor."J.Biol.Chem.. 278. 46029-46034 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Nakano N., Higashiyama S., Ohmoto H., Ishiguro H., Taniguchi N., Wada Y.: "The N-terminal region of NTAK/neuregulin-2 isoforms has an inhibitory activity on angiogenesis."J.Biol.Chem.. 279. 11465-1470 (2004)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Ishiguro H, Sawada H, Nishii K, Yamada K., Nagatsu T.: "Animal models of Huntington's disease."Shinkei Kenkyu no Sinpo. 46. 747-757 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Tsuyoshi Yoshinaka: "Identification and characterization of novel mouse and human ADAM33s with potential metalloprotease activity"Gene. 282. 227-236 (2002)

    • Related Report
      2003 Annual Research Report
  • [Publications] Masanori Asakura: "Cardiac hypertrophy is inhibited by antagonism of ADAM12 processing of HB-EGF : Metalloproteinase inhibitors as a new therapy"Nature Medicine. 8. 35-40 (2002)

    • Related Report
      2003 Annual Research Report
  • [Publications] Naohiro Ichino: "Increase of transcriptional levels of egr-1 and nur77 genes due to both nicotine treatment and withdrawal in pheochromocytoma cells"J.Neural Transmission. 109. 1015-1022 (2002)

    • Related Report
      2003 Annual Research Report
  • [Publications] Hiroshi Ishiguro: "Dopamine neurons are not affected by expanded polyglutamine stretches in HD gene knock-in mice"Advances in Behavioral Biology, Catecholamine Research. 53. 99-102 (2002)

    • Related Report
      2003 Annual Research Report
  • [Publications] Seiji Mori: "PACSIN3 binds ADAM12/meltrin α and up-regulates ectodomain shedding of heparin-binding epidermal growth factor-like growth factor"J.Biological Chemistry. 278. 46029-46034 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Norihiko Nakano: "The N-terminal region of NTAK/neuregulin-2 isoforms has an inhibitory activity on angiogenesis"J.Biological Chemistry. 279. 11465-11470 (2004)

    • Related Report
      2003 Annual Research Report
  • [Publications] Ishiguri H. 他13名: "Age-dependent and tissue-specific CAG repeat instability occurs in mouse knock-in for a mutant Huntington's diseasegene"J.Neurosci.Res.. 65. 289-297 (2001)

    • Related Report
      2002 Annual Research Report
  • [Publications] 石黒啓司: "ハンチントン病モデル動物による神経変性疾患研究の現状"脳と神経. 53. 829-837 (2001)

    • Related Report
      2002 Annual Research Report
  • [Publications] Yoshinaka T. 他7名: "Identification and characterization of novel mouse and human ADAM33s with potential metalloprotease activity"Gene. 282. 227-236 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Asakura 他17名: "Cardiac hypertrophy is inhibited by antagonism of ADAM12 processing of HB-EGF : Metalloprotease inhibitors as a potential new therapy for cardiac hypertrophy"Nature Medicine. 8. 35-40 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Ichino 他5名: "Increase of transcriptional levels of egr-1 and nur77 genes due to both nicotine treatment and withdrawal in pheochrormocytoma cells"J.Neural Transmission. 109. 1015-1022 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Ishiguro 他 名: "Dopamine neurons are not affected by expanded polyglutamine stretches in HD gene knock-in mice"Advances in Behavioral Biology. 53. 99-102 (2002)

    • Related Report
      2002 Annual Research Report

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Published: 2002-04-01   Modified: 2016-04-21  

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