Molecular dissection of mast cell function by using newly generated mast cell lineage specific Cre expressing mice

• Project/Area Number: 15K15157
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Multi-year Fund
• Research Field: Immunology
• Research Institution: Kansai Medical University
• Principal Investigator: MATSUDA Satoshi 関西医科大学, 医学部, 准教授 (00286444)
• Co-Investigator(Renkei-kenkyūsha): WATANABE Toshio 奈良女子大学, 大学院人間文化研究科, 教授 (60201208)
• Research Collaborator: SUMIYOSHI Mami
• Project Period (FY): 2015-04-01 – 2017-03-31
• Project Status: Completed (Fiscal Year 2016)
• Budget Amount: ¥3,770,000 (Direct Cost: ¥2,900,000、Indirect Cost: ¥870,000); Fiscal Year 2016: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2015: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
• Keywords: 遺伝子改変動物 / マスト細胞 / PI3K / シグナル伝達 / 小胞輸送 / マスト細胞分化 / mTORC1 / Arfファミリー

Outline of Final Research Achievements

To understand mast cell biology, we established mast cell lineage specific Cre expressing mice under the control of FcεRIα locus. Among the signaling molecules functioning downstream of PI3K, we focused Tsc1 and Arf1 along with Arf6. Loss of Tsc1, which causes augmentation of mTORC1 signal, led to marked increase of mast cell number in peritoneal cavity. On the other hand, loss of Arf1 along with Arf6, both of which serve as a vesicle trafficking regulator, impaired mast cell development. These results indicate that mTORC1 signal as well as Arf-mediated vesicle trafficking system play a critical role in mast cell development.

Research Products

• [Journal Article] Basigin can be a therapeutic target to restore the retinal vascular barrier function in the mouse model of diabetic retinopathy. (2016)
  • Author(s): Arima, M., Cui, D., Kimura, T., Sonoda, K.H., Ishibashi, T., Matsuda, S., and Ikeda, E.
  • Journal Title: Sci. Rep. Volume: 6 Issue: 1 Pages: 38445-38445
  • DOI: 10.1038/srep38445
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] ADAM12 and ADAM17 are essential molecules for hypoxia-induced impairment of neural vascular barrier function. (2015)
  • Author(s): Cui, D., Arima, M., Takubo, K., Kimura, T., Horiuchi, K., Minagawa, T., Matsuda, S., and Ikeda, E.
  • Journal Title: Sci. Rep. Volume: 5 Issue: 1 Pages: 12796-12796
  • DOI: 10.1038/srep12796
  • Peer Reviewed / Open Access
• [Presentation] マスト細胞脱顆粒過程におけるPI3K経路の役割解明 (2016)
  • Author(s): 松田達志、江口稚佳子、住吉麻実、生田優希、小河穂波、丹賀直美、早川夏姫、渡邊利雄
  • Organizer: 第３９回日本分子生物学会年会
  • Place of Presentation: 横浜（パシフィコ横浜）
  • Year and Date: 2016-11-30
• [Presentation] FcεRIα-Creノックインマウスを用いたマスト細胞機能の解析 (2015)
  • Author(s): 松田達志、江口稚佳子、金光沙也加、渡邊利雄
  • Organizer: 第３８回日本分子生物学会年会・第８８回日本生化学会大会合同大会
  • Place of Presentation: 神戸国際会議場（兵庫県・神戸市）
  • Year and Date: 2015-12-01