Functional analysis of Trib1/2 double knockout mice on hematopoiesis
| Project/Area Number |
23790451
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| Research Category |
Grant-in-Aid for Young Scientists (B)
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| Allocation Type | Multi-year Fund |
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| Research Field |
Experimental pathology
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| Research Institution | Japanese Foundation For Cancer Research |
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Principal Investigator |
YOKOYAMA Takashi 公益財団法人がん研究会, がん研究所発がん研究部, 研究員 (00535833)
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| Project Period (FY) |
2011 – 2012
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| Project Status |
Completed (Fiscal Year 2012)
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| Budget Amount *help |
¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2012: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2011: ¥2,730,000 (Direct Cost: ¥2,100,000、Indirect Cost: ¥630,000)
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| Keywords | Trib1 / Trib2 / C/EBPα / ノックアウトマウス / MAPキナーゼ経路 / 白血病 / 造血 / C/EBPa / 顆粒球分化 / IL6r |
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| Research Abstract |
Overexpression of Trib1 or Trib2 induces acute myeloid leukemia (AML). We have previously reported that enhancement of MAP kinase pathway through interaction of Trib1 with MEK1 and degradation of C/EBPα is required for leukemic activity of Trib1. However Trib1 or Trib2 KO (knockout) mice did not indicate severely abnormal phenotype and it is no clear the Trib1/2 function in normal tissues. In this study, we demonstrated that Trib1 and Trib2 show different expression pattern in many tissues of E13.5 embryo and adult mice. In addition, bone marrow of Trib1 KO mice indicated increase of segmented neutrophils, C/EBPα protein and its target genes that induce granulopoiesis. These results suggest that Trib1 regulates granulopoiesis through degradation of C/EBPα. On the other hand, Trib2 KO mice did not show abnormal differentiation and Trib1/2 double conditional KO indicated the same level of granulopoiesis as Trib1 single KO. In normal bone marrow cells, expression of Trib1 is about 5 fold by compared with Trib2, indicating Trib1 dominantly plays a key role in regulation of granulopoiesis
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Report
(3 results)
Research Products
(17 results)
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[Journal Article] Identification of TRIB1 R107L gain-of-function mutation in human acute megakaryocytic leukemia2012
Author(s)
Yokoyama T, Toki T, Aoki Y, Kanezaki R, Park MJ, Kanno Y, Takahara T, Yamazaki Y, Ito E, Hayashi Y, Nakamura T.
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Journal Title
Blood
Volume: 119
Issue: 11
Pages: 2608-2611
DOI
Related Report
Peer Reviewed
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