A mutation in the translation initiation codon of Gata-1 disrupts megakaryocyte maturation and causes thrombocytopenia
- Majewski, IJ; Metcalf, D; Mielke, LA; Krebs, DL; Ellis, S; Carpinelli, MR; Mifsud, S; Di Rago, L; Corbin, J; Nicola, NA; Hilton, DJ; Alexander, WS;
- Publication Year 2006-09-19,Volume 103,Issue #38,Page 14146-14151
- Journal Title
- PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
- Publication Type
- Journal Article
- We have generated mice from a N-ethyl-N-nitrosourea mutagenesis screen that carry a mutation in the translation initiation codon of Gata-1, termed Plt13, which is equivalent to mutations found in patients with acute megakaryoblastic leukemia and Down syndrome. The Gata-1 locus is present on the X chromosome in humans and in mice. Male mice hemizygous for the mutation (Gata-1(Plt13)/Y) failed to produce red blood cells and died during embryogenesis at a similar stage to Gata-1-null animals. Female mice that carry the Plt13 mutation are mosaic because of random inactivation of the X chromosome. Adult Gata-1(Plt13/+) females were not anemic, but they were thrombocytopenic and accumulated abnormal megakaryocytes without a concomitant increase in megakaryocyte progenitor cells. Gata-1(Plt13/+) mice contained large numbers of blast-like colony-forming cells, particularly in the fetal liver, but also in adult spleen and bone marrow, from which continuous mast cells lines were readily derived. Although the equivalent mutation to Gata-1(Plt13) in humans results in production of GATA-1s, a short protein isoform initiated from a start codon downstream of the mutated initiation codon, Gata-1s was not detected in Gata-1(Plt13/+) mice.
- NATL ACAD SCIENCES
- N-ethyl-N-nitrosourea mutagenesis platelet
- Publisher's Version
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Creation Date: 2006-09-19 12:00:00Last Modified: 2014-12-23 01:45:11