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Molecular and Cellular Biology, June 2005, p. 5205-5214, Vol. 25, No. 12
0270-7306/05/$08.00+0     doi:10.1128/MCB.25.12.5205-5214.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.

The Erythroid Phenotype of EKLF-Null Mice: Defects in Hemoglobin Metabolism and Membrane Stability

Roy Drissen,1 Marieke von Lindern,2 Andrea Kolbus,3,{dagger} Siska Driegen,1 Peter Steinlein,3 Hartmut Beug,3 Frank Grosveld,1 and Sjaak Philipsen*

Department of Cell Biology,1 Department of Hematology Erasmus MC, 3000 DR Rotterdam, The Netherlands,2 Institute of Molecular Pathology, A-1030 Vienna, Austria3

Received 11 January 2005/ Returned for modification 24 February 2005/ Accepted 21 March 2005

Development of red blood cells requires the correct regulation of cellular processes including changes in cell morphology, globin expression and heme synthesis. Transcription factors such as erythroid Krüppel-like factor EKLF (Klf1) play a critical role in erythropoiesis. Mice lacking EKLF die around embryonic day 14 because of defective definitive erythropoiesis, partly caused by a deficit in ß-globin expression. To identify additional target genes, we analyzed the phenotype and gene expression profiles of wild-type and EKLF null primary erythroid progenitors that were differentiated synchronously in vitro. We show that EKLF is dispensable for expansion of erythroid progenitors, but required for the last steps of erythroid differentiation. We identify EKLF-dependent genes involved in hemoglobin metabolism and membrane stability. Strikingly, expression of these genes is also EKLF-dependent in primitive, yolk sac-derived, blood cells. Consistent with lack of upregulation of these genes we find previously undetected morphological abnormalities in EKLF-null primitive cells. Our data provide an explanation for the hitherto unexplained severity of the EKLF null phenotype in erythropoiesis.

* Corresponding author. Mailing address: Erasmus MC, Department of Cell Biology, P.O. Box 1738, 3000 DR Rotterdam, The Netherlands. Phone: 31-10-4088282. Fax: 31-10-4089468. E-mail: j.philipsen{at}erasmusmc.nl.

{dagger} Present address: Dept. of Gynecologic Endocrinology and Reproductive Medicine, University of Vienna Medical School, A-1090 Vienna, Austria.

Molecular and Cellular Biology, June 2005, p. 5205-5214, Vol. 25, No. 12
0022-538X/05/$08.00+0     doi:10.1128/MCB.25.12.5205-5214.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.



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