We have reported that CD1 mice harboring the GATA-1low mutation develop myelofibrosis, a syndrome similar to human idiopathic myelofibrosis, that manifests itself at 12 months of age with marrow fibrosis and with anemia, increased stem/progenitor cell trafficking and extramedullary hemopoiesis in the liver from 15 months onward (

Vannucchi et al., Blood 100: 1123–1132, 2002
). The trait is expressed by homozygote and heterozygote females alike with 100% penetrance. The aim of these experiments was to assess the eventual effects of the genetic background on the severity of the myelofibrotic trait induced by the GATA-1low mutation. To harbour the GATA-1low in different backgrounds, it was exploited the fact that the GATA-1 gene is located on the X chromosome. Therefore, normal C57BL/6 and DBA2 females were crossed with GATA-1low males. Their heterozygote F1 female offspring (50% C57BL/6 or DBA/2, respectively) was backcrossed with wild type males (either C57BL/6 or DBA/2, as appropriate) and the F2 offspring (75% C57BL/6 or DBA72) analysed at 12 (by histological criteria) and at 15 months (by cytofluorimetric criteria) for the expression of the myelofibrotic trait. The results obtained are summarized in the Table below. In summary, all of the mice (independently from the background) developed marrow fibrosis while aging. However, a great variegation was observed in the progression of the disease in the different strains. It is proposed that such a variegation may represent a model to investigate the extreme variability of the clinical picture of the disease in humans.

Summary of the GATA-1low trait in the different backgrounds

C57BL/6CD1DBA2
Perinatal Mortality yes no no 
Thrombocytopenia yes yes yes 
Myelofibrosis    
Anemia no 15 months no 
Tear drop poikilocytes 12 months 15 months no 
Marrow fibrosis yes yes yes 
Osteosclerosis yes limited no 
Progenitor cell trafficking no yes no 
Extramedullary hemopoiesis no yes no 
C57BL/6CD1DBA2
Perinatal Mortality yes no no 
Thrombocytopenia yes yes yes 
Myelofibrosis    
Anemia no 15 months no 
Tear drop poikilocytes 12 months 15 months no 
Marrow fibrosis yes yes yes 
Osteosclerosis yes limited no 
Progenitor cell trafficking no yes no 
Extramedullary hemopoiesis no yes no 
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Topics:
gata1 protein, human, genetic background, mutation, myelofibrosis, fibrosis, anemia, myelofibrosis, idiopathic, chronic, osteosclerosis, thrombocytopenia, mice, inbred c57bl

Author notes

Corresponding author

2005, The American Society of Hematology
2004
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