EKLF and KLF2 have compensatory roles in embryonic β-globin gene expression and primitive erythropoiesis

被引:49
作者
Basu, Priyadarshi
Lung, Tina K.
Lemsaddek, Wafaa
Sargent, Thanh Giang
Williams, David C., Jr.
Basu, Mohua
Redmond, Latasha C.
Lingrel, Jerry B.
Haar, Jack L.
Lloyd, Joyce A.
机构
[1] Virginia Commonwealth Univ, Massey Canc Ctr, Dept Human Genet, Goodwin Res Lab, Richmond, VA 23298 USA
[2] Virginia Commonwealth Univ, Dept Anat & Neurobiol, Richmond, VA 23298 USA
[3] Virginia Commonwealth Univ, Dept Pathol, Richmond, VA 23298 USA
[4] Univ Cincinnati, Coll Med, Dept Mol Genet Biochem & Microbiol, Cincinnati, OH 45267 USA
关键词
D O I
10.1182/blood-2006-11-057307
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
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 beta h1-, but not adult beta-globin, 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 beta h1-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.
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收藏
页码:3417 / 3425
页数:9
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