| Budget Amount *help |
¥3,770,000 (Direct Cost: ¥2,900,000、Indirect Cost: ¥870,000)
Fiscal Year 2016: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2015: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2014: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
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| Outline of Final Research Achievements |
GFI1B is an essential transcription factor for megakaryocyte and erythrocyte development. We performed whole exome sequencing and identified a novel GFI1B mutation in a family with congenital macrothrombocytopenia, and a decreased number of platelet α-granules and abnormally shaped red blood cells. An immunofluorescence analysis revealed decreased thrombospondin-1 and increased CD34 expression in platelets from the patient. The mutant was unable to repress the expression of the reporter gene and had a dominant-negative effect over wild-type GFI1B. In addition, the mutation abolished recognition of a consensus-binding site in gel shift assays. Furthermore, transduction of mouse fetal liver-derived megakaryocytes with the mutant resulted in the production of abnormally large proplatelet tips, which were reduced in number. Our study provides further proof of concept that GFI1B is an essential protein for the normal development of the megakaryocyte lineage.
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