Suppressor screen in Mpl(-/-) mice: c-Myb mutation causes supraphysiological production of platelets in the absence of thrombopoietin signaling
Details
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
Abstract
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.
Publisher
NATL ACAD SCIENCES
Keywords
GENETIC SCREENS; PRIMARY REGULATOR; ENU MUTAGENESIS; GENOME-WIDE; V-MYB; MPL; MOUSE; RECEPTOR; MEGAKARYOCYTOPOIESIS; HEMATOPOIESIS
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Creation Date: 2004-04-27 12:00:00
Last Modified: 0001-01-01 12:00:00
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