• Search Research Projects
  • Search Researchers
  • How to Use
  1. Back to previous page

Cytokine receptor γc chain/Jak3 mediated signal transduction and analysis of immunodeficiecy by dysfunction of the γc chain/Jak3

Research Project

Project/Area Number 12470075
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Immunology
Research InstitutionShinshu University

Principal Investigator

TAKESHITA Toshikazu  Shinshu University School of Medicine, Microbiology and Immunology, Professor, 医学部, 教授 (60212023)

Co-Investigator(Kenkyū-buntansha) ISHII Naoto  Tohoku University, School of Medicine, Research Associate, 医学系研究科, 助手 (60291267)
Project Period (FY) 2000 – 2001
Project Status Completed (Fiscal Year 2001)
Budget Amount *help
¥14,300,000 (Direct Cost: ¥14,300,000)
Fiscal Year 2001: ¥6,700,000 (Direct Cost: ¥6,700,000)
Fiscal Year 2000: ¥7,600,000 (Direct Cost: ¥7,600,000)
KeywordsIL-2 receptor / γc chain / Jak3 / SCID / STAM1 / STAM2 / Hgs / Graf40
Research Abstract

We identified and have characterized the interleukin 2 receptor γ chain (IL-2Rγ ), of which mutations cause Human X-linked severe combined immunodeficiency disease ( XSCID ), a disease that occurs in as many as 50 % of patients with primary SCID. It was found that mutations of Jak3, which is associated with and mediates the down stream signal transduction from the γ chain, also caused autosomal recessive SCID. Thus, we considered the possibility that there is the novel gene related to SCID down stream of Jak3 and then originally identified novel Jak3 substrates including STAM. In this study, using the gene targeting and transgenic mice we analyzed the in vivo function of the molecules to determine its involvement in the signal transduction pathway from γ chain /Jak3.
( 1 ) Double deficient mice, lacking both STAM1 and STAM2, were embryonically lethal. To further elucidate the function of STAM in lymphocytes, we established conditionally targeting mice that will lack of both molecules in lymphocytes
( 2 ) Hgs knockout ( KO ) mice showed significantly decreased response to stimulation with transforming growth factor-β ( TGF-β ) family molecules.
( 3 ) AMSH-deficient mice exhibited postnatal growth, retardation and died between day 19 and 23. The neurons were defect in the subfield of hippocampus of AMSH-deficient mice.
( 4 ) The total number of thymocytes were reduced in the transgenic mice expressing Graf40 mutant, whereas it was significantly increased in the double-negative thymocytes subset.

Report

(3 results)
  • 2001 Annual Research Report   Final Research Report Summary
  • 2000 Annual Research Report
  • Research Products

    (6 results)

All Other

All Publications (6 results)

  • [Publications] Kikuchi, K., et al.: "Suppression of tymic development by the dominant-negative form of Gads"Int. Immunol. 13. 777-783 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Yamada, M., et al.: "Loss of hippocampal CA3 pyramidal neurons in mice lacking STAM1"Mol. Cell. Biol.. 21. 3807-3819 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Kikuchi, K., et al.: "Suppression of thymic development by the dominant-negative form of Gads"Int. Immunol. 13. 777-783 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Yamada, M., et al.: "Loss of hippocampal CA3 pyramidal neurons in mice lacking STAM1"Mol. Cell. Biol.. 21. 3807-3819 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Endo,K., et al.: "STAM2, a new member of the STAM family, binding to the Janus kinases."FEBS Letters. 477. 55-61 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Miura,S., et al.: "Hgs (Hrs), a FYVE domain protein, is involved in Smad signaling through cooperation with SARA."Mol.Cell.Biol.. 20. 9346-9355 (2000)

    • Related Report
      2000 Annual Research Report

URL: 

Published: 2000-04-01   Modified: 2016-04-21  

Information User Guide FAQ News Terms of Use Attribution of KAKENHI

Powered by NII kakenhi