Model mouse for human specific xeno-autoantigen inflammation

• Project/Area Number: 16K15235
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Multi-year Fund
• Research Field: Pathological medical chemistry
• Research Institution: Kyoto University
• Principal Investigator: Takematsu Hiromu 京都大学, 医学研究科, 特定教授 (80324680)
• Research Collaborator: Laine Roger Louisiana State University, Prof.
• Project Period (FY): 2016-04-01 – 2018-03-31
• Project Status: Completed (Fiscal Year 2017)
• Budget Amount: ¥3,640,000 (Direct Cost: ¥2,800,000、Indirect Cost: ¥840,000); Fiscal Year 2017: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2016: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
• Keywords: シアル酸 / 自己抗原免疫応答 / 異種抗原 / ヒト / 動物 / 慢性炎症 / 病態モデル / マウスモデル / 進化 / 異種自己抗原 / 炎症 / 自己免疫応答 / 免疫応答 / 病態 / 化合物 / 糖鎖 / 免疫学

Outline of Final Research Achievements

Sialic acid occupies outmost surface of cells, which would be direct access to the extracellular space to the cell. Human lacks N-glycolylneraminic acid, a molecular species of sialic acid. Although humans are not able to make N-glycolylneuramic acid, they could utilize it when supplied. Thus N-glycolylneuraminic acid could cause a autoimmunity. Here, fundamental experiments are carried out to develop human model of this auto antigen immunity in mice.

Academic Significance and Societal Importance of the Research Achievements

本研究は、未だ、謎の多い、ほぼヒトでしかおこらない異種自己抗原応答状態をマウスで再現するために基盤的な結果を得た。現在まで、様々なマウスを使った実験系が、ヒトの病気との関連で解析されている。今回つくったマウスは、ヒト疾患を念頭に置いてマウスモデルを使用する際には、幅広く標準的背景となるべき状態であると考えられる。

Research Products

• [Int'l Joint Research] Louisiana State University(米国)
• [Int'l Joint Research] Utrecht University(オランダ)
• [Int'l Joint Research] Louisiana State University(米国)
• [Journal Article] Ribosomal protein uS7/Rps5 serine-223 in protein kinase-mediated phosphorylation and ribosomal small subunit maturation (2018)
  • Author(s): Tomioka Makoto、Shimobayashi Mitsugu、Kitabatake Makoto、Ohno Mutsuhito、Kozutsumi Yasunori、Oka Shogo、Takematsu Hiromu
  • Journal Title: SCIENTIFIC REPORT Volume: 8 Issue: 1 Pages: 1244-1244
  • DOI: 10.1038/s41598-018-19652-z
  • NAID: 120006510286
  • Peer Reviewed / Open Access
• [Journal Article] Proximity labeling of cis-ligands of CD22/Siglec-2 reveals stepwise α2,6 sialic acid-dependent and -independent interactions. (2018)
  • Author(s): Alborzian Deh Sheikh A, Akatsu C, Imamura A, Abdu-Allah HHM, Takematsu H, Ando H, Ishida H, Tsubata T
  • Journal Title: Biochem Biophys Res Commun. Volume: 495 Issue: 1 Pages: 854-859
  • DOI: 10.1016/j.bbrc.2017.11.086
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Ecm33 is a novel factor involved in efficient glucose uptake for nutrition-responsive TORC1 signaling in yeast. (2017)
  • Author(s): Umekawa M, Ujihara M, Nakai D, Takematsu H, Wakayama M.
  • Journal Title: FEBS Lett. Volume: 591 Issue: 22 Pages: 3721-3729
  • DOI: 10.1002/1873-3468.12882
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] UPS40 gene knockdown disrupts glomerular permwability in zebrafish. (2017)
  • Author(s): Takagi H, Nishibori Y, Katayama K, Katada T, Takahashi S, Kikuchi Z, Takahashi SI, Kamei H, Kawakami H, Akimoto Y, Kudo A, Asanuma K, Takematsu H, Yan K.
  • Journal Title: Am J Physiol Renal Physiol. Volume: 312 Issue: 4 Pages: 702-715
  • DOI: 10.1152/ajprenal.00197.2016
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Physiological Exploration of the Long-term Evolutionary Selection Against Expression of N-glycolylneuraminic Acid in the Brain (2017)
  • Author(s): Naito-Matsui Y, Davies LR, Takematsu H, Chou HH, Tangvoranuntakul P, Carlin AF, Verhagen A, Heyser CJ, Yoo SW, Choudhury B, Paton JC, Paton AW, Varki NM, Schnaar RL, Varki A
  • Journal Title: J Biol Chem. Volume: 292(7) Issue: 7 Pages: 2557-2570
  • DOI: 10.1074/jbc.m116.768531
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Psychosine-triggered endomitosis is modulated by membrane sphingolipids through regulation of phosphoinositide 4,5-bisphosphate production at the cleavage furrow. (2016)
  • Author(s): Watanabe H, Okahara K, Naito-Matsui Y, Abe M, Go S, Inokuchi J, Okazaki T,Kobayashi T, Kozutsumi Y, Oka S, Takematsu H.
  • Journal Title: Mol Biol Cell. Volume: 27 Issue: 13 Pages: 2037-2050
  • DOI: 10.1091/mbc.e15-08-0555
  • Peer Reviewed / Open Access
• [Journal Article] The signaling pathways underlying starvation-induced upregulation of α-mannosidase Ams1 in Saccharomyces cerevisiae (2016)
  • Author(s): Umekawa M, Ujihara M, Makishima K, Yamamoto S, Takematsu H, Wakayama M.
  • Journal Title: Biochim Biophys Acta. Volume: 1860 Issue: 6 Pages: 1192-1201
  • DOI: 10.1016/j.bbagen.2016.02.018
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Presentation] 胚中心B細胞による糖鎖変化の意義 (2017)
  • Author(s): 竹松弘
  • Organizer: 糖鎖免疫Glyco-Immunology2017
  • Place of Presentation: 東京医科歯科大学・東京
  • Year and Date: 2017-01-25
  • Invited
• [Presentation] Induction of “endomitosis” by psychosine is controlled by membrane glycosphingolipids and cluster of sphingomyelin (2017)
  • Author(s): Watanabe H, Itani Y, Kobayashi T. Oka S. ○Takematsu H
  • Organizer: 2017 Sphingolipid club meeting XII
  • Int'l Joint Research
• [Presentation] Psychosine-mediated “endomitosis” induction is controlled by membrane glycosphingolipid and sphingomyelin cluster (2017)
  • Author(s): Watanabe H, Itani Y, Kobayashi T. Oka S. ○Takematsu H
  • Organizer: 2017 FASEB symposium on Lysophospholipid and related mediators (poster)
  • Int'l Joint Research
• [Presentation] Identification of Modifier Gene That Modulate Cell Surface P-selectin Ligand Expression (2016)
  • Author(s): Kano Y, Fujinawa R, Kitagawa H, Okuno Y, Kannagi R, Oka S and ○Takematsu H
  • Organizer: 2016 International Carbohydrate Symposium
  • Place of Presentation: Marriott Hotel, New Orleans, USA
  • Year and Date: 2016-07-18
  • Int'l Joint Research
• [Presentation] リゾスフィンゴ糖脂質サイコシンによるエンドマイトーシスとPIP2ドメインの抑制 (2016)
  • Author(s): ○渡邉寛，小林俊秀，岡昌吾，竹松弘
  • Organizer: 第89回日本生化学大会
  • Place of Presentation: 東北大学・仙台市
  • Year and Date: 2016-06-26
• [Presentation] リゾスフィンゴ糖脂質サイコシンは、分裂溝におけるPIP2の産生を抑制することでエンドマイトーシスを誘導する (2016)
  • Author(s): ○渡邉寛，小林俊秀，岡昌吾，竹松弘
  • Organizer: 生化学会近畿支部会
  • Place of Presentation: 神戸薬科大学・神戸市
  • Year and Date: 2016-05-15
• [Presentation] Psychosine-triggered endomitosis to produce multiploid cells (2016)
  • Author(s): Takematsu H
  • Organizer: 2016 Korea-Japan Bioactive Lipid Joint Symposium
  • Place of Presentation: Bereve Hotel, Jeju, Korea
  • Year and Date: 2016-05-12
  • Int'l Joint Research / Invited
• [Presentation] Dynamic regulation of Siglec-ligands on activated lymphocytes (2016)
  • Author(s): Takematsu H
  • Organizer: Glycoscience Japan-The Netherlands Joint Seminar
  • Place of Presentation: Leiden University Medical Center, Leiden, the Netherlands
  • Year and Date: 2016-04-20
  • Int'l Joint Research / Invited
• [Remarks] 京都大学人間健康科学生化学教室
  • URL: http://oka-lab.hs.med.kyoto-u.ac.jp/
• [Remarks] 竹松研究室
  • URL: http://oka-lab.hs.med.kyoto-u.ac.jp/concept3.html