| First Author | Basu P | Year | 2007 |
| Journal | Blood | Volume | 110 |
| Issue | 9 | Pages | 3417-25 |
| PubMed ID | 17675555 | Mgi Jnum | J:149115 |
| Mgi Id | MGI:3847623 | Doi | 10.1182/blood-2006-11-057307 |
| Citation | Basu P, et al. (2007) EKLF and KLF2 have compensatory roles in embryonic beta-globin gene expression and primitive erythropoiesis. Blood 110(9):3417-25 |
| abstractText | The Kruppel-like C2/H2 zinc finger transcription factors (KLFs) control development and differentiation. Erythroid Kruppel-like factor (EKLF or KLF1) regulates adult beta-globin gene expression and is necessary for normal definitive erythropoiesis. KLF2 is required for normal embryonic Ey- and betah1-, but not adult betaglobin, gene expression in mice. Both EKLF and KLF2 play roles in primitive erythroid cell development. To investigate potential interactions between these genes, EKLF/KLF2 double-mutant embryos were analyzed. EKLF(-/-)KLF2(-/-) mice appear anemic at embryonic day 10.5 (E10.5) and die before E11.5, whereas single-knockout EKLF(-/-) or KLF2(-/-) embryos are grossly normal at E10.5 and die later than EKLF(-/-)KLF2(-/-) embryos. At E10.5, Ey- and betah1-globin mRNA is greatly reduced in EKLF(-/-)KLF2(-/-), compared with EKLF(-/-) or KLF2(-/-) embryos, consistent with the observed anemia. Light and electron microscopic analyses of E9.5 EKLF(-/-)KLF2(-/-) yolk sacs, and cytospins, indicate that erythroid and endothelial cells are morphologically more abnormal than in either single knockout. EKLF(-/-)KLF2(-/-) erythroid cells are markedly irregularly shaped, suggesting membrane abnormalities. EKLF and KLF2 may have coordinate roles in a common progenitor to erythroid and endothelial cells. The data indicate that EKLF and KLF2 have redundant functions in embryonic beta-like globin gene expression, primitive erythropoiesis, and endothelial development. |
