Development of myelofibrosis in mice genetically impaired for GATA-1 expression (GATA-1low mice)

Alessandro Maria Vannucchi, Lucia Bianchi, Cristina Cellai, Francesco Paoletti, Rosa Alba Rana, Rodolfo Lorenzini, Giovanni Migliaccio, Anna Rita Migliaccio

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199 Scopus citations


The phenotype induced by the GATA-1low (neoδHS) mutation is here further characterized by analyzing the hemopoietic system during the aging (up to 20 months) of a GATA-1low colony (135 mutants and 40 normal littermates). Mutants expressed normal hematocrit values (Hct = 45.9 ± 4.0) until 12 months but became anemic from 15 months on (Hct = 30.9 ± 3.9; P < .05). Anemia was associated with several markers of myelofibrosis such as the presence of tear-drop poikilocytes and progenitor cells in the blood, collagen fibers in the marrow and in the spleen, and hemopoietic foci in the liver. Semi- quantitative reverse transcription-polymerase chain reaction showed that growth factor genes implicated in the development of myelofibrosis (such as osteocalcin, transforming growth factor-β1, platelet-derived growth factor, and vascular endothelial growth factor) were all expressed in the marrow from the mutants at higher levels than in corresponding normal tissues. The GATA-1low mutants experienced a slow progression of the disease because the final exitus was not observed until at least 15 months with a probability of survival more favorable than that of W/Wv mice concurrently kept in the animal facility (P < .001, by Kaplan-Meier analysis). In conclusion, impaired GATA-1 expression may contribute to the development of myelofibrosis, and the GATA-1low mutants may represent a suitable animal model for the human disease that may shed light on its pathogenesis.

Original languageEnglish
Pages (from-to)1123-1132
Number of pages10
Issue number4
StatePublished - 15 Aug 2002
Externally publishedYes


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