Phenotypes of the various Gata1 gene-targeted mice
Name of line . | Effect on GATA-1 . | Phenotype . | Mouse/human pathology . |
|---|---|---|---|
| GATA-1 null | No GATA-1 expression in any tissue | Midgestation lethality due to anemia (E10.5) | |
| GATA-1 knock-down (ΔneoΔHS) | Wild-type levels of GATA-1 in erythroid cells; no detectable expression in megakaryocytes | Thrombocytopenia with a significant increase in megakaryocyte numbers in the spleen and bone marrow | |
| GATA-1low (neoΔHS) | Erythroid expression decreased 5-fold; megakaryocytic expression not detectable | Most die during embryogenesis. About 5% of the hemizygous males are born anemic and thrombocytopenic. The few animals that survive recover from anemia but remain thrombocytopenic. Surviving mice develop anemia with extramedullary hematopoiesis and spleen and bone marrow fibrosis around 15 mo. Mice also exhibit defects in mast cell maturation. | Myelofibrosis |
| GATA-1.05 | Erythroid expression decreased 20-fold; megakaryocytic expression not detectable | Hemizygous males die by E12.5 of anemia. Heterozygous females exhibit anemia and thrombocytopenia and begin to die by 5 mo. | Myelodysplastic syndrome |
| GATA-1 Val205Gly | GATA-1 is expressed normally, but cannot interact with its essential cofactor FOG-1 | Hemizygous males die of anemia by E12.5. | Congenital dyserythropoietic anemia and thrombocytopenia |
| ΔdblGATA | Insufficient expression in eosinophil precursors* | Selective loss of the eosinophil lineage | |
| GATA-1 AMKL mutant | Express GATA-1s in lieu of full length GATA-1 | To be determined | TMD and/or DS-AMKL (?) |
Name of line . | Effect on GATA-1 . | Phenotype . | Mouse/human pathology . |
|---|---|---|---|
| GATA-1 null | No GATA-1 expression in any tissue | Midgestation lethality due to anemia (E10.5) | |
| GATA-1 knock-down (ΔneoΔHS) | Wild-type levels of GATA-1 in erythroid cells; no detectable expression in megakaryocytes | Thrombocytopenia with a significant increase in megakaryocyte numbers in the spleen and bone marrow | |
| GATA-1low (neoΔHS) | Erythroid expression decreased 5-fold; megakaryocytic expression not detectable | Most die during embryogenesis. About 5% of the hemizygous males are born anemic and thrombocytopenic. The few animals that survive recover from anemia but remain thrombocytopenic. Surviving mice develop anemia with extramedullary hematopoiesis and spleen and bone marrow fibrosis around 15 mo. Mice also exhibit defects in mast cell maturation. | Myelofibrosis |
| GATA-1.05 | Erythroid expression decreased 20-fold; megakaryocytic expression not detectable | Hemizygous males die by E12.5 of anemia. Heterozygous females exhibit anemia and thrombocytopenia and begin to die by 5 mo. | Myelodysplastic syndrome |
| GATA-1 Val205Gly | GATA-1 is expressed normally, but cannot interact with its essential cofactor FOG-1 | Hemizygous males die of anemia by E12.5. | Congenital dyserythropoietic anemia and thrombocytopenia |
| ΔdblGATA | Insufficient expression in eosinophil precursors* | Selective loss of the eosinophil lineage | |
| GATA-1 AMKL mutant | Express GATA-1s in lieu of full length GATA-1 | To be determined | TMD and/or DS-AMKL (?) |
Predicted effect of targeting of the palindromic GATA-1 site within the GATA-1 promoter.62