Loss of hematopoietic mucin-type O-glycan causes thrombocytopenia in mice

2014 Fiscal Year Final Research Report

• Project/Area Number: 24300152
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Partial Multi-year Fund
• Section: 一般
• Research Field: Laboratory animal science
• Research Institution: University of Tsukuba
• Principal Investigator: KUDO Takashi 筑波大学, 医学医療系, 准教授 (20288062)
• Co-Investigator(Kenkyū-buntansha): TAKAHASHI Satoru 筑波大学, 医学医療系, 教授 (50271896)
• Project Period (FY): 2012-04-01 – 2015-03-31
• Keywords: 動物 / 糖鎖 / 発生・分化 / 血小板

Outline of Final Research Achievements

Mucin function has been difficult to characterize because its structure and synthesis are complex. To address the biological role of mucin-type O-glycans in hematopoietic cells, we conditionally ablated C1galt, which is essential for synthesis of mucin-type O-glycans. Inducible, Mx1-cre-mediated C1galt conditional knockout (Mx1-C1) mice exhibited severe thrombocytopenia, giant platelets, and prolonged bleeding times.There were few proplatelets in cultured Mx1-C1 primary megakaryocytes. Moreover, the expression of hypoglycosylated GpIbα protein in Mx1-C1 megakaryocytes and platelets was greatly reduced despite the fact that expression of gpIbα transcript was unchanged. Our observations indicate that O-glycan is required for terminal megakaryocyte differentiation and platelet production and that the decrease in GpIbα in cells lacking O-glycan may be caused by increased proteolysis.

Free Research Field

生化学