Function of sugar chain in congenital muscular dystrophy

• Project/Area Number: 26860682
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Neurology
• Research Institution: Tokyo Metropolitan Geriatric Hospital and Institute of Gerontology
• Principal Investigator: Yamada Takeyuki 地方独立行政法人東京都健康長寿医療センター(東京都健康長寿医療センター研究所), 東京都健康長寿医療センター研究所, 研究員 (40725199)
• Project Period (FY): 2014-04-01 – 2016-03-31
• Project Status: Completed (Fiscal Year 2015)
• Budget Amount: ¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000); Fiscal Year 2015: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000); Fiscal Year 2014: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
• Keywords: O-マンノース型糖鎖 / 糖鎖修飾 / 神経分化 / 幹細胞

Outline of Final Research Achievements

O-mannose-type glycosylation of a-dystroglycan (a-DG) is required for its extracellular matrix binding activities. Aberrant a-DG glycosylation causes congenital muscular dystrophy (CMD), accompanying neurological and ocular abnormalities. Here, we identified novel mutations in POMGNT1, which encodes an essential component in O-mannosylation pathway, in retinitis pigmentosa. Enzymatic assay showed that the mutants POMGNT1 impaired its enzymatic activities, with only 10 to 30% of the wild type level retained. On the other hand, mutants POMGNT1 identified from CMD nearly abolished its enzymatic activities. These results suggest that a few O-mannose-type glycosylation syntheses suppress CMD, but develop RP.

Research Products

• [Journal Article] Mutations in POMGNT1 cause non-syndromic retinitis pigmentosa. (2016)
  • Author(s): Mingchu Xu, Takeyuki Yamada, Zixi Sun, Aiden Eblimit, Irma Lopez, Feng Wang, Hiroshi Manya, Shan Xu, Li Zhao, Yumei Li, Adva Kimchi, Dror Sharon, Ruifang Sui, Tamao Endo, Robert K. Koenekoop, Rui Chen
  • Journal Title: Hum. Mol. Genet. Volume: 25 Issue: 8 Pages: 1479-1488
  • DOI: 10.1093/hmg/ddw022
  • Peer Reviewed / Int'l Joint Research / Acknowledgement Compliant
• [Presentation] POMGNT1の変異が網膜色素変性症を引き起こす (2016)
  • Author(s): 山田健之, 萬谷博, Mingchu Xu, Rui Chen, 遠藤玉夫
  • Organizer: 第39回日本基礎老化学会大会
  • Place of Presentation: 伊勢原市民文化会館（神奈川県・伊勢原市）
  • Year and Date: 2016-05-27