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

The phenotype induced by the GATA-1low (neoHS) mutation is here further charac-terized by analyzing the hemopoietic sys-tem 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 sev-eral 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–poly-merase chain reaction showed that growth factor genes implicated in the develop-ment of myelofibrosis (such as osteocal-cin, transforming growth factor-1, plate-let-derived growth factor, and vascular endothelial growth factor) were all ex-pressed 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 develop-ment of myelofibrosis, and the GATA-1low mutants may represent a suitable animal model for the human disease that may shed light on its pathogenesis. (Blood