title: Runx3 deficiency results in myeloproliferative disorder in aged mice.
abstract: The RUNX family genes encode transcription factors that are involved in development and human diseases. RUNX1 is one of the most frequently mutated genes in human hematological malignancies and is a critical factor for the generation and maintenance of hematopoietic stem cells. Another Runx family gene, Runx3, is known to be expressed in hematopoietic cells. However, its involvement in hematopoiesis remains unclear. Here we show the hematopoietic phenotypes in Runx3 conditional knockout (KO) mice (Runx3(fl/fl);Mx1-Cre(+)): whereas young Runx3 KO mice did not exhibit any significant hematopoietic defects, aged Runx3 KO mice developed a myeloproliferative disorder characterized by myeloid-dominant leukocytosis, splenomegaly, and an increase of hematopoietic stem/progenitor cells (HSPCs). Notably, Runx3-deficient cells showed hypersensitivity to granulocyte-colony stimulating factor, suggesting enhanced proliferative and mobilization capability of Runx3-deficient HSPCs when stimulated. These results suggest that, besides Runx1, Runx3 also plays a role in hematopoiesis.
authors.affiliation: Institute of Molecular and Cell Biology, Singapore.
authors.forename: Chelsia Qiuxia
authors.initials: CQ
authors.lastname: Wang
authors.forename: Lena
authors.initials: L
authors.lastname: Motoda
authors.forename: Masanobu
authors.initials: M
authors.lastname: Satake
authors.forename: Yoshiaki
authors.initials: Y
authors.lastname: Ito
authors.forename: Ichiro
authors.initials: I
authors.lastname: Taniuchi
authors.forename: Vinay
authors.initials: V
authors.lastname: Tergaonkar
authors.forename: Motomi
authors.initials: M
authors.lastname: Osato
mesh_terms: D000375:Aging / Q000097:blood / Q000235:genetics / Q000502:physiology*; D000818:Animals; D002465:Cell Movement / Q000187:drug effects / Q000235:genetics; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D050677:Core Binding Factor Alpha 3 Subunit / Q000172:deficiency / Q000235:genetics*; D018014:Gene Transfer Techniques; D016179:Granulocyte Colony-Stimulating Factor / Q000494:pharmacology; D006410:Hematopoiesis / Q000187:drug effects / Q000235:genetics* / Q000502:physiology; D006412:Hematopoietic Stem Cells / Q000187:drug effects / Q000473:pathology / Q000502:physiology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009196:Myeloproliferative Disorders / Q000235:genetics* / Q000473:pathology
chemical_list: D050677:Core Binding Factor Alpha 3 Subunit; C493730:Runx3 protein, mouse; D016179:Granulocyte Colony-Stimulating Factor