The development and demonstration of methodology to elucidate the sugar chain function and glycosyltransferase knockout mouse phenotype.

• Project/Area Number: 23500493
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Laboratory animal science
• Research Institution: Kanazawa University
• Principal Investigator: SUGIHARA Kazushi 金沢大学, 医学系, 技術専門職員 (10377418)
• 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): 2011 – 2013
• Project Status: Completed (Fiscal Year 2013)
• Budget Amount: ¥5,200,000 (Direct Cost: ¥4,000,000、Indirect Cost: ¥1,200,000); Fiscal Year 2013: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2012: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2011: ¥2,470,000 (Direct Cost: ¥1,900,000、Indirect Cost: ¥570,000)
• Keywords: 発生工学 / 遺伝子改変動物 / 糖鎖生物学

Research Abstract

From behavioral analyses of beta 1, 4-galactosyltransferase-2 (B4GalT-2) gene knockout mice, we have found that galactose sugar chains synthesized by B4GalT-2 have a function in the central nervous system. Therefore, we tried to generate novel knock-in mice in order to identify cells and brain regions where B4GalT-2 is involved, to obtain clues identifying functional carbohydrate molecules. We constructed two kinds of targeting vectors, one for monitoring B4GalT-2 expression by lacZ gene and the other for recovering B4GalT-2 expression conditionally. We are trying to isolate desired ES clones.

Research Products

• [Journal Article] EXTL2, a member of the EXT family of tumor suppressors, controls glycosaminoglycan biosynthesis in a xylose kinase-dependent manner (2013)
  • Author(s): Nadanaka, S., Zhou, S., Kagiyama, S., Shoji, N., Sugahara, K., Sugihara, K., Asano, M.and Kitagawa, H.
  • Journal Title: The Journal of Biological Chemistry Volume: 288 Pages: 9321-9333
  • DOI: 10.1074/jbc.m112.416909
  • Peer Reviewed
• [Journal Article] Large-scale identification of target proteins of a glycosyltransferase isozyme by Lectin-IGOT-LC/MS, an LC/MS-based glycoproteomic approach. (2012)
  • Author(s): Sugahara, D., Kaji, H., Sugihara, K., Asano, M., and Narimatsu, H.
  • Journal Title: Scientif ic Reports Volume: 2 Pages: 680-680
  • DOI: 10.1038/srep00680
  • Peer Reviewed
• [Journal Article] Essential role of endothelial class II PI3K-C2α in angiogenesis and vascular barrier function. (2012)
  • Author(s): Yoshioka K, Yoshida K, Cui H, Wakayama T, Takuwa N, Okamoto Y, Du W, Qi X, Asanuma K, Sugihara K, Aki S, Miyazawa H, Biswas K, Nagakura C, Ueno M, Iseki S, Schwartz JR, Okamoto H, Sasaki T,Matsui O, Asano M, Adams HR, Takakura N, Takuwa Y.
  • Journal Title: Nat Med Volume: 18 Pages: 1560-1569
  • DOI: 10.1038/nm.2928
  • Peer Reviewed
• [Journal Article] Glycoprotein Hyposialylation Gives Rise to a Nephrotic-Like Syndrome That Is Prevented by Sialic Acid Administration in GNE V572L Point-Mutant Mice. (2012)
  • Author(s): Ito, M., Sugihara, K., Asaka, T., Toyama, T., Yo sh ih ar a, T., Furuichi, K., Wada, T. and Asano, M.
  • Journal Title: PLoS One Volume: 7 Pages: 1-13
  • DOI: 10.1371/journal.pone.0029873
  • Peer Reviewed
• [Journal Article] Specific enzyme complex of beta-1,4-galactosyltransferase-II and glucuronyltransferase-P facilitates biosynthesis of N-linked human natural killer-1 (HNK-1) carbohydrate. (2011)
  • Author(s): N. Nakagawa, T. Yoshihara, M. Asano, and S. Oka
  • Journal Title: J Biol Chem. Volume: 286(36) Pages: 31337-31346
  • DOI: 10.1074/jbc.m111.233353
  • Peer Reviewed
• [Presentation] GNE V572L 点変異マウスにおける腎臓の病態解析とシアル酸糖鎖の関与 (2011)
  • Author(s): 伊藤光俊ら
  • Organizer: 第84回日本生化学会大会
  • Place of Presentation: 国立京都国際会館（京都府）
• [Presentation] Hyposialylation of glycoproteins in the UDP-N-acetylglucosamine-2-epimerase/N-acetylmannosamine kinase (GNE) point mutant mice gives rise to a renal impairment that is prevented by sialic acid administration (2011)
  • Author(s): Ito, M et al.
  • Organizer: Kidney Week 2011
  • Place of Presentation: Pennsylvania Convention Center (USA)
• [Remarks]
  • URL: http://kiea.w3.kanazawa-u.ac.jp/tglab/tganimHP/Top.html