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Status |
Public on Feb 14, 2007 |
Title |
The molecular consequences of Nix ablation on apoptosis and erythropoiesis |
Organism |
Mus musculus |
Experiment type |
Expression profiling by array
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Summary |
Normal erythropoiesis requires a critical balance between proapoptotic and antipaoptotic pathways. Bcl-xl, an antiapoptotic protein is induced at end-stages of differentiation of erythroid precursors in response to erythropoietin. The details of the proapoptotic pathway and the critical proapoptotic proteins inhibited by Bcl-xl in erythropoiesis are not well understood. We employed gene targeting to ablate Nix, a proapoptotic BH3-domain only Bcl2 family protein, which is known to be transcriptionally induced during erythropoiesis. Nix null mice exhibited reticulocytosis and thrombocytosis in the peripheral blood; and profound splenomegaly with erythroblastosis in the spleen and bone marrow despite normal erythropoietin levels and blood oxygen tension. In vivo apoptosis was diminished in erythroblast precursors from Nix null spleens. To define the molecular consequences of Nix ablation on apoptosis and erythropoiesis, we conducted a detailed comparative analysis of gene expression in spleens from 8 week old Nix null mice and wild type controls. Of 45,101 genes analyzed, 514 were significantly upregulated and 386 down-regulated in Nix-/- splenocytes. Functional cluster analysis delineated the ten most highly regulated gene sets, revealing increased levels of cell cycle and erythroid genes, with decreased levels of cell death and B-cell genes. Keywords: strain comparison
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Overall design |
In the study, we hybridized RNA from 8 week old spleens of wild type (WT) control and Nix null mice (Nix-/-) to Affymetrix MOE430A GeneChip® arrays containing 45,101 well characterized mouse genes/ESTs.
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Citation(s) |
17420462 |
Submission date |
Feb 13, 2007 |
Last update date |
Feb 11, 2019 |
Contact name |
Bruce J Aronow |
E-mail(s) |
bruce.aronow@chmcc.org
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Phone |
513-636-4865
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Organization name |
Cincinnati Children's Hospital Medical Center
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Street address |
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City |
Cincinnati |
State/province |
OH |
ZIP/Postal code |
45229 |
Country |
USA |
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Platforms (1) |
GPL1261 |
[Mouse430_2] Affymetrix Mouse Genome 430 2.0 Array |
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Samples (8)
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Relations |
BioProject |
PRJNA98367 |