title: Murine tribbles homolog 2 deficiency affects erythroid progenitor development and confers macrocytic anemia on mice.
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.
authors.affiliation: Institute of Biomedical Sciences, Academia Sinica, Taipei, Taiwan.|Taiwan Mouse Clinic, Academia Sinica, Taipei, Taiwan.
authors.forename: Kou-Ray
authors.initials: KR
authors.lastname: Lin
authors.affiliation: Institute of Molecular Biology, Academia Sinica, Taipei, Taiwan.
authors.forename: Hsin-Fang
authors.initials: HF
authors.lastname: Yang-Yen
authors.affiliation: Institute of Cellular and Organismic Biology, Academia Sinica, Taipei, Taiwan.
authors.forename: Huang-Wei
authors.initials: HW
authors.lastname: Lien
authors.affiliation: Institute of Biological Chemistry, Academia Sinica, Taipei, Taiwan.
authors.forename: Wei-Hao
authors.initials: WH
authors.lastname: Liao
authors.affiliation: Institute of Biological Chemistry, Academia Sinica, Taipei, Taiwan.
authors.forename: Chang-Jen
authors.initials: CJ
authors.lastname: Huang
authors.affiliation: Department of Clinical Laboratory Science and Medical Biotechnology, School of Medicine, National Taiwan University, Taipei, Taiwan.
authors.forename: Liang-In
authors.initials: LI
authors.lastname: Lin
authors.affiliation: Genomic Research Center, Academia Sinica, Taipei, Taiwan.
authors.forename: Chung-Leung
authors.initials: CL
authors.lastname: Li
authors.affiliation: Institute of Biomedical Sciences, Academia Sinica, Taipei, Taiwan.|Taiwan Mouse Clinic, Academia Sinica, Taipei, Taiwan.|Institute of Molecular Medicine, School of Medicine, National Taiwan University, Taipei, Taiwan.
authors.forename: Jeffrey Jong-Young
authors.initials: JJ
authors.lastname: Yen
mesh_terms: D000748:Anemia, Macrocytic / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D000818:Animals; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000235:genetics / Q000378:metabolism; D015672:Erythroid Precursor Cells / Q000378:metabolism* / Q000473:pathology; D004920:Erythropoiesis / Q000235:genetics*; D005786:Gene Expression Regulation; D006461:Hemolysis; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000172:deficiency* / Q000235:genetics / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D017346:Protein Serine-Threonine Kinases / Q000037:antagonists & inhibitors* / Q000172:deficiency / Q000378:metabolism; D015027:Zebrafish
chemical_list: D047908:Intracellular Signaling Peptides and Proteins; C515847:tribbles 2 protein, mouse; D017346:Protein Serine-Threonine Kinases; D017871:Calcium-Calmodulin-Dependent Protein Kinases; C489044:TRIB2 protein, human