Suppressor screen in Mpl(-/-) mice: c-Myb mutation causes supraphysiological production of platelets in the absence of thrombopoietin signaling
- Carpinelli, MR; Hilton, DJ; Metcalf, D; Antonchuk, JL; Hyland, CD; Mifsud, SL; Di Rago, L; Hilton, AA; Willson, TA; Roberts, AW; Ramsay, RG; Nicola, NA; Alexander, WS;
Publication Year 2004-04-27, Volume 101, Issue #17, Page 6553-6558
- Journal Title
- PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
- Publication Type
- Journal Article
- Genetic screens in lower organisms, particularly those that identify modifiers of preexisting genetic defects, have been used success-fully to order components of complex signaling pathways. To date, similar suppressor screens have not been used in vertebrates. To define the molecular pathways regulating platelet production, we have executed a large-scale modifier screen with genetically thrombocytopenic Mpi(-/-) mice by using N-ethyl-N-nitrosourea mutagenesis. Here we show that mutations in the c-Myb gene cause a myeloproliferative syndrome and supraphysiological expansion of megakaryocyte and platelet production in the absence of thrombopoietin signaling. This screen demonstrates the utility of large-scale N-ethyl-N-nitrosourea mutagenesis suppressor screens in mice for the simultaneous discovery and in vivo validation of targets for therapeutic discovery in diseases for which mouse models are available.
- NATL ACAD SCIENCES
- GENETIC SCREENS; PRIMARY REGULATOR; ENU MUTAGENESIS; GENOME-WIDE; V-MYB; MPL; MOUSE; RECEPTOR; MEGAKARYOCYTOPOIESIS; HEMATOPOIESIS
- Publisher's Version
- Rights Notice
- Refer to copyright notice on published article.
Creation Date: 2004-04-27 12:00:00Last Modified: 0001-01-01 12:00:00