Basic studies of immunoligocal function using sphingolipid-deficient mice

• Project/Area Number: 24570145
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Functional biochemistry
• Research Institution: Azabu University
• Principal Investigator: YAMASHITA Tadashi 麻布大学, 獣医学部, 教授 (30220338)
• Project Period (FY): 2012-04-01 – 2015-03-31
• Project Status: Completed (Fiscal Year 2014)
• Budget Amount: ¥5,590,000 (Direct Cost: ¥4,300,000、Indirect Cost: ¥1,290,000); Fiscal Year 2014: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000); Fiscal Year 2013: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2012: ¥2,860,000 (Direct Cost: ¥2,200,000、Indirect Cost: ¥660,000)
• Keywords: スフィンゴ脂質 / 遺伝子改変動物 / モデルマウス / スフィンゴ糖脂質 / ノックアウトマウス

Outline of Final Research Achievements

T cell specific deletion using gene deficient mice of sphingolipids demonstrated the complete loss of them in peripheral blood stream. Previous studies demonstrated that GM3 knockout mice showed rheumatism become early onset and aggravated. The total deletion of sphingolipids and GM3, one molecule of sphingolipids showed little difference. On the other hand, a remarkable difference was observed in the colitis model mice. This suggests that amount of ceramide and ceramide-derivatives in cytoplasm participate colitis resistant phenotype of sphingolipids-dificient mice.

Research Products

• [Journal Article] Inhibition of GM3 synthase attenuates neuropathology of niemann-pick disease type C by affecting sphingolipid metabolism. (2014)
  • Author(s): Lee. H., Lee. JK., Bae. YC., Yang. SH., Okino. N., Schuchman. EH., Yamashita. T., Bae. JS., Jin. HK.
  • Journal Title: Mol Cells. Volume: 37 Pages: 161-171
  • Peer Reviewed / Open Access
• [Journal Article] Depletion of gangliosides enhances cartilage degradation in mice. (2014)
  • Author(s): Sasazawa F, Onodera T, Yamashita T, Seito N, Tsukuda Y, Fujitani N, Shinohara Y, Iwasaki N.
  • Journal Title: Osteoarthritis Cartilage. Volume: 22 Pages: 313-322
  • Peer Reviewed / Open Access
• [Journal Article] Depletion of gangliosides enhances cartilage degradation in mice. (2014)
  • Author(s): Sasazawa F, Onodera T, Yamashita T, Seito N, Tsukuda Y, Fujitani N, Shinohara Y, Iwasaki N.
  • Journal Title: Osteoarthritis Cartilage. Volume: 22(2) Pages: 313-22
  • Peer Reviewed
• [Journal Article] Improvement of spontaneous alternation behavior deficit by activation of α4β2 nicotinic acetylcholine receptor signaling in the ganglioside GM3-deficient mice. (2013)
  • Author(s): Niimi, K., Nishioka, C., Miyamoto, T., Takahashi, E,. Miyoshi I., Itakura, C., Yamashita, T.
  • Journal Title: Biomed Res Volume: 34(４) Pages: 189-195
  • Peer Reviewed
• [Journal Article] Activin receptor-like kinase5 inhibition suppresses mouse melanoma by ubiquitin degradation of Smad4, thereby derepressing eomesodermin in cytotoxic T lymphocytes. (2013)
  • Author(s): Yoon JH, Jung SM, Park SH, Kato M, Yamashita T, Lee IK, Sudo K, Nakae S, Han JS, Kim OH, Oh BC, Sumida T, Kuroda M, Ju JH, Jung KC, Park SH, Kim DK, Mamura M.
  • Journal Title: EMBO Mol Med. Volume: 5(11) Pages: 1720-39
  • Peer Reviewed