Table 1:

Animal models of Gata1 deficiencies

Genotype	Hematopoietic phenotype	Reference
Gata1ΔIE (erythroid first exon (IE) deleted)	Gata1ΔIE mRNA level is significantly down-regulated in the megakaryocyte lineage but is expressed in the erythroid lineage. These Gata1ΔIE mRNA fail to produce full-length GATA1 protein, but instead generate GATA1 lacking the N-terminal domain inefficiently. Hemizygous male embryos die by E12.5 showing severe anemia. Conditional knockout male mice (3–4 weeks) suffer from severe thrombocytopenia and anemia. Nucleated erythrocytes can be found on the peripheral blood smear. Splenomegaly with apparent destruction of the splenic architecture, due to expansion of the red pulp, can be observed. Markedly increased CD41+CD61+ megakaryocytes and accumulation of CD71hiTer119low in the bone marrow can be detected by flow cytometric analysis.	111
Gata1ΔN (Δ 3–63 AA) and Gata1Δe2 (Δ 1–83 AA)	Adult hemizygotes have normal RBC, PLT, normal spleen structure and normal numbers of megakaryocytes in spleen. 10–15% of the mutant mice were lost in utero. Fetal liver pallor and reduced cellularity (by ∼50%) can be observed in E12.5 embryos from hemizygous and homozygous compared to the wild type. At E12.5 more CD41+ cells can be detected by flow cytometric analysis, and megakaryocytes are hyperproliferative in liquid medium containing thrombopoietin. Erythroid colony-forming units (CFU-Es) in Gata1ΔN fetal liver are reduced by ∼50%. At E14.5 and thereafter, Gata1ΔN fetal liver had normal cellularity and comparable Ter119+ cells as wild type.	110
Gata1− (Start codon Disrupted)	Male embryos die between E10.5-E11.5 of gestation because of severe anemia. Female heterozygotes are born pale and recover after birth. Embryonic erythroid cells are arrested at an early proerythroblast-like stage of their development and die thereafter by apoptosis. Abundant acetylcholinesterase positive cells can be found in methylcellulose culture supplemented with Epo and kit ligand.	20
Gata1low or Gata1neoΔHS (Disrupt DNase I-hypersensitive region by replacing ∼8 kb of upstream sequences, including the IT and HS regions, with a PGK-NeoR cassette flanked by loxP sites)	Yolk sac erythropoiesis and fetal erythropoiesis are disturbed. Embryos are pale or dead by E13.5–14.5 and definitive erythroid cells are largely arrested at the proerythroblast stage of development. CFU-E and BFU-E are morphologically abnormal in colony forming assay with fetal liver cells. About 5% of hemizygous males survive fetal anemia into adult life. Abnormal nucleated erythroid precursors and erythrocytes can be found in peripheral blood smears of newborns, but anemia phenotypes at birth disappear by 4–5 weeks after birth. Mutant mice also loss of megakaryocyte GATA1 expression, resulting in markedly reduced PLT associated with deregulated megakaryocyte proliferation and severely impaired maturation. Female mice heterozygous have normal platelet numbers, but with increased megakaryocytes in hematopoietic tissues.	22,112
Gata1.05 (Introduce a neo cassette into the intergenic region between an important regulatory region of the erythroid promoter and the mRNA cap site)	The expression of GATA1 mRNA in the mutant male embryos is less than 5% of the level present in wild-type embryos (E9.5). The yolk sacs of mutant males are pale and almost no blood vessels are present. Embryos die in utero due to impaired primitive erythropoiesis. There are decreased number of erythroid cells and CFU-E in mutant fetal livers.	15,113