Functional analysis of Trib1/2 double knockout mice on hematopoiesis

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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