Table 1.
Genes critical in primitive erythropoiesis as demonstrated by null mutation.
| Gene | EryP phenotype of null mutant embryos |
|---|---|
| Klf1/Eklf | EryP show abnormal membranes with ruffled surfaces, abnormal expression of adhesion molecules, and loss of appropriate maturation markers. |
| Klf2 | Embryonic lethality: Irregular shape of EryP with abnormal pseudopodia present. Reduced globin gene expression. |
| Klf1;Klf2 | Klf1; Klf2 compound null mutant embryos show a more severe defect than either single null mutant. |
| Runx1 | Embryonic lethality; EryP show abnormal “dimples” in their cell membranes. EryP-CFC numbers unaffected. Ter-119 expression reduced by half. |
| Gata1 | EryP progenitors appear arrested in development and are more proliferative than wild-type progenitors. |
| Gata1; Gata2 | Compound Gata1; Gata2 null mutant mice show a more severe EryP defect than single mutants. Primitive erythropoiesis is functionally absent. No βH1 globin gene is detectible in compound mutant embryos. |
| Sox6 | Loss of inhibition of embryonic globin expression in EryD. Large, nucleated, embryonic globin-expressing cells present in circulation late in gestation. |
| Gsn (gelsolin) | Abnormal morphology and increase in circulating binucleated and βH1-expressing cells. |
| miR-126 | EBs lacking miR-126 fail to support erythropoiesis. Function is via VCAM1+ supporting mesenchymal cells. |
| c-Myc | EpoR-Cre mice used to delete c-Myc in erythroid cells die at E12.5. Primitive erythroblasts show accelerated maturation presenting as orthochromatophilic erythroblasts when wild-type animals show basophilic erythroblasts. Nuclear condensation is accelerated in c-Myc null EryP. |
| Abc-me/Abcb10 | Fail of EryP to proliferate, increased ROS and apoptosis. |
| Ldb1 | Primitive erythropoieis absent from the E9.0 YS. No erythroid cells generated from Ldb1−/− ES cell cultures. |
| Fog1 | EryP fail to mature and differentiate. Appear as immature megaloblastic and basophilic erythroblasts at E11.5. |
| Epo Receptor | Fewer EryP are present at E9.5. |
| Brg1 | YS devoid of EryP at E9.5 due to apoptosis. |
| p400/Domino | EryP-CFC absent. |
| Mdm2 | Mice lacking the p53-inhibitor Mdm2, but not Mdm4, develop apoptotic EryP and die at E13.5. |
| Adult hemoglobin | Deletion of both adult α- and β-globin genes leads to thalassemic EryP and embryonic lethality at E13.5. |
References for each mutant mouse strain are in main body of text.