title: Ikaros increases normal apoptosis in adult erythroid cells.
abstract: Ikaros is a critical transcriptional regulator of hematopoietic cell differentiation. In addition to its effects on the lymphoid system and hematopoietic stem-cell compartment, we have previously shown that Ikaros is also required for normal erythroid development. In this report, we compare Ikaros-dependent gene expression in erythroid cells of mice lacking the Ikaros protein with that of normal mice in purified adult bone-marrow erythroid cells (BMRC). Gene expression, measured by Affymetrix microarray analysis, indicates that in the BMRC of Ikaros-null mice, there is significant up-regulation of SMADs 6 and 7, serine protease inhibitor 3, and immediate-early protein 3 (IER3), all proteins that play a modulating role in apoptosis. We investigate the role of Ikaros in oxidative stress-induced apoptosis using Annexin-V staining and FACS analysis. We find a decrease in apoptosis in the BMRC of Ikaros-null mice compared to normal mice. This effect is also seen in nonerythroid cells but is stronger in BMRC. We conclude that normal Ikaros function increases normal apoptosis in erythroid cells. The data also suggest that Ikaros plays a role in apoptosis-mediated events in other normal hematopoietic cell lineages.
authors.affiliation: Department of Medicine, Columbia University, New York, NY, USA.
authors.forename: Dianne
authors.initials: D
authors.lastname: Pulte
authors.forename: Rocio A
authors.initials: RA
authors.lastname: Lopez
authors.forename: Shane T
authors.initials: ST
authors.lastname: Baker
authors.forename: Maureen
authors.initials: M
authors.lastname: Ward
authors.forename: Ellen
authors.initials: E
authors.lastname: Ritchie
authors.forename: Christine A
authors.initials: CA
authors.lastname: Richardson
authors.forename: David W
authors.initials: DW
authors.lastname: O'Neill
authors.forename: Arthur
authors.initials: A
authors.lastname: Bank
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000502:physiology*; D015672:Erythroid Precursor Cells / Q000166:cytology / Q000502:physiology*; D004920:Erythropoiesis; D005434:Flow Cytometry; D020869:Gene Expression Profiling / Q000379:methods; D051740:Ikaros Transcription Factor / Q000096:biosynthesis* / Q000172:deficiency; D051379:Mice; D018345:Mice, Knockout; D020411:Oligonucleotide Array Sequence Analysis / Q000379:methods; D018384:Oxidative Stress / Q000502:physiology; D015854:Up-Regulation / Q000502:physiology*
chemical_list: C497238:Zfpn1a1 protein, mouse; D051740:Ikaros Transcription Factor