All mice harboring the X-linked Gata1low mutation in a predominantly CD1 background are born anemic and thrombocytopenic. They recover from anemia at 1 month of age but remain thrombocytopenic all their life and develop myelofibrosis, a syndrome similar to human idiopathic myelofibrosis, at 12 months. The effects of the genetic background on the myelofibrosis developed by Gata1low mice was assessed by introducing the mutation, by standard genetic approaches, in the C57BL/6 and DBA/2 backgrounds and by analyzing the phenotype of the different mutants at 12 to 13 (by histology) and 16 to 20 (by cytofluorimetry) months of age. Although all the Gata1 low mice developed fibrosis at 12 to 13 months, variegations were observed in the severity of the phenotype expressed by mutants of different backgrounds. In C57BL/6 mice, the mutation was no longer inherited in a Mendelian fashion, and fibrosis was associated with massive osteosclerosis. Instead, DBA/2 mutants, although severely anemic, expressed limited fibrosis and osteosclerosis and did not present tear-drop poikilocytes in blood or extramedullary hemopoiesis in liver up to 20 months of age. We propose that the variegation in myelo-fibrosis expressed by Gata1low mutants of different strains might represent a model to study the variability of the clinical picture of the human disease. © 2005 by The American Society of Hematology.
CITATION STYLE
Martelli, F., Ghinassi, B., Panetta, B., Alfani, E., Gatta, V., Pancrazzi, A., … Migliaccio, A. R. (2005). Variegation of the phenotype induced by the Gata1low mutation in mice of different genetic backgrounds. Blood, 106(13), 4102–4113. https://doi.org/10.1182/blood-2005-03-1060
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