Budget Amount *help |
¥17,680,000 (Direct Cost: ¥13,600,000、Indirect Cost: ¥4,080,000)
Fiscal Year 2014: ¥5,330,000 (Direct Cost: ¥4,100,000、Indirect Cost: ¥1,230,000)
Fiscal Year 2013: ¥5,200,000 (Direct Cost: ¥4,000,000、Indirect Cost: ¥1,200,000)
Fiscal Year 2012: ¥7,150,000 (Direct Cost: ¥5,500,000、Indirect Cost: ¥1,650,000)
|
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.
|