RGD Reference Report - Leukemogenesis caused by incapacitated GATA-1 function. - Rat Genome Database

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Leukemogenesis caused by incapacitated GATA-1 function.

Authors: Shimizu, R  Kuroha, T  Ohneda, O  Pan, X  Ohneda, K  Takahashi, S  Philipsen, S  Yamamoto, M 
Citation: Shimizu R, etal., Mol Cell Biol. 2004 Dec;24(24):10814-25.
RGD ID: 10450734
Pubmed: PMID:15572684   (View Abstract at PubMed)
PMCID: PMC533998   (View Article at PubMed Central)
DOI: DOI:10.1128/MCB.24.24.10814-10825.2004   (Journal Full-text)

GATA-1 is essential for the development of erythroid and megakaryocytic lineages. We found that GATA-1 gene knockdown female (GATA-1.05/X) mice frequently develop a hematopoietic disorder resembling myelodysplastic syndrome that is characterized by the accumulation of progenitors expressing low levels of GATA-1. In this study, we demonstrate that GATA-1.05/X mice suffer from two distinct types of acute leukemia, an early-onset c-Kit-positive nonlymphoid leukemia and a late-onset B-lymphocytic leukemia. Since GATA-1 is an X chromosome gene, two types of hematopoietic cells reside within heterozygous GATA-1 knockdown mice, bearing either an active wild-type GATA-1 allele or an active mutant GATA-1.05 allele. In the hematopoietic progenitors with the latter allele, low-level GATA-1 expression is sufficient to support survival and proliferation but not differentiation, leading to the accumulation of progenitors that are easily targeted by oncogenic stimuli. Since such leukemia has not been observed in GATA-1-null/X mutant mice, we conclude that the residual GATA-1 activity in the knockdown mice contributes to the development of the malignancy. This de novo model recapitulates the acute crisis found in preleukemic conditions in humans.

RGD Manual Disease Annotations    Click to see Annotation Detail View
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
myelodysplastic syndrome  ISOGata1 (Mus musculus)10450734; 10450734 RGD 
myelodysplastic syndrome  IMP 10450734 RGD 

Objects Annotated

Genes (Rattus norvegicus)
Gata1  (GATA binding protein 1)

Genes (Mus musculus)
Gata1  (GATA binding protein 1)

Genes (Homo sapiens)
GATA1  (GATA binding protein 1)


Additional Information