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ZFIN ID: ZDB-PUB-160824-3
Murine tribbles homolog 2 deficiency affects erythroid progenitor development and confers macrocytic anemia on mice
Lin, K.R., Yang-Yen, H.F., Lien, H.W., Liao, W.H., Huang, C.J., Lin, L.I., Li, C.L., Yen, J.J.
Date: 2016
Source: Scientific Reports   6: 31444 (Journal)
Registered Authors: Huang, Chang-Jen
Keywords: Apoptosis, Haematopoiesis
MeSH Terms:
  • Anemia, Macrocytic/genetics
  • Anemia, Macrocytic/metabolism*
  • Anemia, Macrocytic/pathology
  • Animals
  • Calcium-Calmodulin-Dependent Protein Kinases/genetics
  • Calcium-Calmodulin-Dependent Protein Kinases/metabolism
  • Erythroid Precursor Cells/metabolism*
  • Erythroid Precursor Cells/pathology
  • Erythropoiesis/genetics*
  • Gene Expression Regulation
  • Hemolysis
  • Humans
  • Intracellular Signaling Peptides and Proteins/deficiency*
  • Intracellular Signaling Peptides and Proteins/genetics
  • Intracellular Signaling Peptides and Proteins/metabolism
  • Mice
  • Mice, Knockout
  • Protein-Serine-Threonine Kinases/antagonists & inhibitors*
  • Protein-Serine-Threonine Kinases/deficiency
  • Protein-Serine-Threonine Kinases/metabolism
  • Zebrafish
PubMed: 27550848 Full text @ Sci. Rep.
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ABSTRACT
Tribbles homolog 2 (Trib2) is a member of Tribbles protein pseudokinases and involves in apoptosis, autoimmunity, cancer, leukemia and erythropoiesis, however, the physiological function of Trib2 in hematopoietic system remains to be elucidated. Here, we report that Trib2 knockout (KO) mice manifest macrocytic anemia and increase of T lymphocytes. Although Trib2 deficient RBCs have similar half-life as the control RBCs, Trib2 KO mice are highly vulnerable to oxidant-induced hemolysis. Endogenous Trib2 mRNA is expressed in early hematopoietic progenitors, erythroid precursors, and lymphoid lineages, but not in mature RBCs, myeloid progenitors and granulocytes. Consistently, flow cytometric analysis and in vitro colony forming assay revealed that deletion of Trib2 mainly affected erythroid lineage development, and had no effect on either granulocyte or megakaryocyte lineages in bone marrow. Furthermore, a genetic approach using double knockout of Trib2 and C/ebpα genes in mice suggested that Trib2 promotes erythropoiesis independent of C/ebpα proteins in vivo. Finally, ectopic expression of human Trib2 in zebrafish embryos resulted in increased expression of erythropoiesis-related genes and of hemoglobin. Taking all data together, our results suggest that Trib2 positively promotes early erythrocyte differentiation and is essential for tolerance to hemolysis.
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