A mutation in the translation initiation codon of Gata-1 disrupts megakaryocyte maturation and causes thrombocytopenia Academic Article uri icon


  • 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-1Plt13/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-1Plt13/+ females were not anemic, but they were thrombocytopenic and accumulated abnormal megakaryocytes without a concomitant increase in megakaryocyte progenitor cells. Gata-1Plt13/+ 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-1Plt13 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-1Plt13/+ mice.


  • 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 date

  • September 19, 2006