title: Critical role of P1-Runx1 in mouse basophil development.
abstract: Runx1(P1N/P1N) mice are deficient in the transcription factor distal promoter-derived Runt-related transcription factor 1 (P1-Runx1) and have a > 90% reduction in the numbers of basophils in the BM, spleen, and blood. In contrast, Runx1(P1N/P1N) mice have normal numbers of the other granulocytes (neutrophils and eosinophils). Although basophils and mast cells share some common features, Runx1(P1N/P1N) mice have normal numbers of mast cells in multiple tissues. Runx1(P1N/P1N) mice fail to develop a basophil-dependent reaction, IgE-mediated chronic allergic inflammation of the skin, but respond normally when tested for IgE- and mast cell-dependent passive cutaneous anaphylaxis in vivo or IgE-dependent mast cell degranulation in vitro. These results demonstrate that Runx1(P1N/P1N) mice exhibit markedly impaired function of basophils, but not mast cells. Infection with the parasite Strongyloides venezuelensis and injections of IL-3, each of which induces marked basophilia in wild-type mice, also induce modest expansions of the very small populations of basophils in Runx1(P1N/P1N) mice. Finally, Runx1(P1N/P1N) mice have normal numbers of the granulocyte progenitor cells, SN-Flk2(+/-), which can give rise to all granulocytes, but exhibit a > 95% reduction in basophil progenitors. The results of the present study suggest that P1-Runx1 is critical for a stage of basophil development between SN-Flk2(+/-) cells and basophil progenitors.
authors.affiliation: Department of Pathology, Stanford University School of Medicine, Stanford, CA 94305, USA.
authors.forename: Kaori
authors.initials: K
authors.lastname: Mukai
authors.forename: Maya J
authors.initials: MJ
authors.lastname: BenBarak
authors.forename: Masashi
authors.initials: M
authors.lastname: Tachibana
authors.forename: Keigo
authors.initials: K
authors.lastname: Nishida
authors.forename: Hajime
authors.initials: H
authors.lastname: Karasuyama
authors.forename: Ichiro
authors.initials: I
authors.lastname: Taniuchi
authors.forename: Stephen J
authors.initials: SJ
authors.lastname: Galli
mesh_terms: D000818:Animals; D001491:Basophils / Q000166:cytology* / Q000502:physiology*; D001854:Bone Marrow Cells / Q000166:cytology / Q000502:physiology; D002452:Cell Count; D050676:Core Binding Factor Alpha 2 Subunit / Q000235:genetics* / Q000502:physiology*; D004804:Eosinophils / Q000166:cytology / Q000502:physiology; D005260:Female; D006374:Helminthiasis, Animal / Q000276:immunology; D006412:Hematopoietic Stem Cells / Q000166:cytology / Q000502:physiology; D007154:Immune System Diseases / Q000235:genetics* / Q000503:physiopathology; D008297:Male; D008407:Mast Cells / Q000166:cytology / Q000502:physiology; D051379:Mice; D008810:Mice, Inbred C57BL; D008817:Mice, Mutant Strains; D009504:Neutrophils / Q000166:cytology / Q000502:physiology; D010641:Phenotype; D013154:Spleen / Q000166:cytology / Q000502:physiology
chemical_list: D050676:Core Binding Factor Alpha 2 Subunit; C493726:Runx1 protein, mouse