Characterization of AEP/Legumain-deficient mice as a model of hemophagocytic syndrome-like disease

• Project/Area Number: 18500325
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Laboratory animal science
• Research Institution: Kanazawa University
• Principal Investigator: HASHIMOTO Noriyoshi Kanazawa University, 学際科学実験センター, 准教授 (50242524)
• Co-Investigator(Kenkyū-buntansha): ASANO Masahide 金沢大学, 学際科学実験センター, 教授 (50251450)
• Project Period (FY): 2006 – 2008
• Project Status: Completed (Fiscal Year 2008)
• Budget Amount: ¥4,100,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥600,000); Fiscal Year 2008: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2007: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2006: ¥1,500,000 (Direct Cost: ¥1,500,000)
• Keywords: 病態モデル / 血球貪食症候群 / Legumain / AEP / リソソーム蓄積症 / プロテアーゼ / リソソーム病 / 遺伝子改変動物 / 血液疾患 / 疾患モデルマウス / レグマイン / 実験動物

Research Abstract

アスパラギンエンドペプチダーゼ(AEP)遺伝子欠損マウスを解析し, 体温上昇, 貧血, 肝脾腫, 骨髄や脾臓における血球貪食細胞の出現など, ヒト血球貪食症候群(HPS)の病態をよく再現したモデルマウスとして位置づけた。血球貪食細胞はマクロファージであり赤血球貪食能は上昇し, 一部でリソソーム病であるゴーシェ病に特徴的なゴーシェ細胞様の特徴も示した。リソソーム酵素であるAEPの欠損により貪食作用の亢進と血球分解産物の異常な蓄積を生じ, HPS様病態形成に深く関わっていることが示唆された。

Research Products

• [Journal Article] Mice lacking asparaginyl endopeptidase develop disorders resembling hemophagocytic syndrome (2009)
  • Author(s): Chi-Bun Chan, Michiyo Abe, Noriyoshi Hashimoto, Chunhai Hao, Ifor R. Williams, Xia Liu, Shinji Nakao, Akitsugu Yamamoto, Chengyun Zheng, Jan-Inge Henter, Marie Meeths, Magnus Nordenskjold, Shi-Yong Li, Ikuko Hara-Nishimura, Masahide Asano, Keqiang Ye
  • Journal Title: Proc Natl Acad Sci U S A 106(2) Pages: 468-473
  • Peer Reviewed
• [Journal Article] Mice lacking asparaginyl endopeptidase develop disorders resembling hemophagocytic syndrome. (2009)
  • Author(s): Chan, C. B., Abe, M., Hashimoto, N., et al.
  • Journal Title: Proceeding of the National Academy of Sciences of the United States of America 106 Pages: 468-473
  • Peer Reviewed
• [Journal Article] Neuroprotective actions of PIKE-L by inhibition of SET proteolytic degradation by asparagine endopeptidase (2008)
  • Author(s): Zhixue Liu, Sung-Wuk Jang, Xia Liu, Dongmei Cheng, Junmin Peng, Manuel Yepes, Xiao-jiang Li, Steve Matthews, Colin Watts, Masahide Asano, Ikuko Hara-Nishimura, Hongbo R. Luo, Keqiang Ye
  • Journal Title: Mol Cell 29(6) Pages: 665-678
  • Peer Reviewed
• [Journal Article] Neuroprotective actions of PIKE-L by inhibition of SET proteolytic degradation by asparagine endopeptidase (2008)
  • Author(s): Liu Z, et. al.
  • Journal Title: Molecular Cell 29 Pages: 665-678
  • Peer Reviewed
• [Journal Article] Legumain/asparaginyl endopeptidase controls extracellular matrix remodeling through the degradation of fibronectin in mouse renal proximal tubular cells (2007)
  • Author(s): Yoshikata Morita, Hisazumi Araki, Toshiro Sugimoto, Keisuke Takeuchi, Takuya Yamane, Toshinaga Maeda, Yoshio Yamamoto, Katsuji Nishi, Masahide Asano, Kanae Shirahama-Noda, Mikio Nishimura, Takashi Uzu, Ikuko Hara-Nishimura, Daisuke Koya, Atsunori Kashiwagi, Iwao Ohkubo
  • Journal Title: FEBS Lett 581(7) Pages: 1417-1424
  • Peer Reviewed
• [Journal Article] Legumain/asparaginyl endopeptidase controls extracellular matrix remodeling through the degradation of fibronectin in mouse renal proximal tubular cells (2007)
  • Author(s): Morita Y, et. al.
  • Journal Title: FEBS Letter 581 Pages: 1417-1424
  • Peer Reviewed
• [Presentation] AEP/Legumain欠損マウスにおける血球貪食症候群様病態の解析 (2007)
  • Author(s): 安陪道代、橋本憲佳、宮石理、中尾眞二、西村いくこ、浅野雅秀
  • Organizer: 第30回日本分子生物学会年会・第80回日本生化学会大会合同大会
  • Place of Presentation: 横浜
• [Presentation] Legumain(AEP)遺伝子欠損マウスは血球貪食症候群様の病態を呈する (2006)
  • Author(s): 安陪道代, 橋本憲佳, 宮石理, 西村いくこ, 浅野雅秀
  • Organizer: 第53回日本実験動物学会
  • Place of Presentation: 神戸