Functional characterization of a novel GFI1B mutation causing congenital macrothrombocytopenia.
| Project/Area Number |
26860840
|
|---|
| Research Category |
Grant-in-Aid for Young Scientists (B)
|
| Allocation Type | Multi-year Fund |
|---|
| Research Field |
Pediatrics
|
|---|
| Research Institution | National Hospital Organization Nagoya Medical Center |
|---|
Principal Investigator |
Kitamura Katsumasa 独立行政法人国立病院機構(名古屋医療センター臨床研究センター), その他部局等, 客員研究員 (40724381)
|
|---|
| Project Period (FY) |
2014-04-01 – 2017-03-31
|
| Project Status |
Completed (Fiscal Year 2016)
|
| 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)
|
|---|
| Keywords | 先天性血小板減少症 / 巨大血小板 / 転写因子 / 巨核球分化 / 赤芽球分化 / 巨核球系分化 / 赤芽球系分化 |
|---|
| 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.
|
Report
(4 results)
Research Products
(7 results)
-
[Journal Article] Functional characterization of a novel GFI1B mutation causing congenital macrothrombocytopenia2016
Author(s)
Kitamura K, Okuno Y, Yoshida K, Sanada M, Shiraishi Y, Muramatsu H, Kobayashi R, Furukawa K, Miyano S, Kojima S, Ogawa S, Kunishima S
-
Journal Title
J Thromb Haemost
Volume: 14
Issue: 7
Pages: 1462-9
DOI
Related Report
Peer Reviewed
-
-
-
-
[Presentation] Functional Characterization of a Novel GFI1B Mutation Causing Congenital Macrothrombocytopenia2015
Author(s)
Katsumasa Kitamura, Yusuke Okuno, Kenichi Yoshida, Masashi Sanada, Yuichi Shiraishi, Hideki Muramatsu, Ryoji Kobayashi, Satoru Miyano, Seiji Kojima, Seishi Ogawa, Shinji Kunishima
Organizer
第57回米国血液学会
Place of Presentation
米国、オーランド
Year and Date
2015-12-05
Related Report
Int'l Joint Research
-
-
