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This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Sinclair, A. M. Articles by Scheuermann, R. H. Search for Related Content PubMed PubMed Citation Articles by Sinclair, A. M. Articles by Scheuermann, R. H. Related Collections Hematopoiesis and Stem Cells Immunobiology Apoptosis Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  Blood, 15 December 2001, Vol. 98, No. 13, pp. 3658-3667 HEMATOPOIESIS Lymphoid apoptosis and myeloid hyperplasia in CCAAT displacement protein mutant mice Angus M. Sinclair, Jamie A. Lee, Adrian Goldstein, Dongxia Xing, Shengxi Liu, Ruzeng Ju, Philip W. Tucker, Ellis J. Neufeld, and Richard H. Scheuermann From the Department of Pathology and Laboratory of Molecular Pathology, University of Texas Southwestern Medical Center, Dallas; Division of Hematology/Oncology, Children's Hospital, Department of Pediatrics, Harvard Medical School, Boston, MA; and Department of Microbiology and Institute for Cellular and Molecular Biology, University of Texas at Austin. CCAAT displacement protein (cux/CDP) is an atypical homeodomain protein that represses expression of several developmentally regulated lymphoid and myeloid genes in vitro, including gp91-phox, immunoglobulin heavy chain, the T-cell receptor  and  chains, and CD8. To determine how this activity affects cell development in vivo, a hypomorphic allele of cux/CDP was created by gene targeting. Homozygous mutant mice (cux/CDPHD/HD) demonstrated a partial neonatal lethality phenotype. Surviving animals suffered from a wasting disease, which usually resulted in death between 2 and 3 weeks of age. Analysis of T lymphopoiesis demonstrated that cux/CDPHD/HD mice had dramatically reduced thymic cellularity due to enhanced apoptosis, with a preferential loss of CD4+CD8+ thymocytes. Ectopic CD25 expression was also observed in maturing thymocytes. B lymphopoiesis was also perturbed, with a 2- to 3-fold reduction in total bone marrow B-lineage cells and a preferential loss of cells in transition from pro-B/pre-BI to pre-BII stages due to enhanced apoptosis. These lymphoid abnormalities were independent of effects related to antigen receptor rearrangement. In contrast to the lymphoid demise, cux/CDPHD/HD mice demonstrated myeloid hyperplasia. Bone marrow reconstitution experiments identified that many of the hematopoietic defects were linked to microenvironmental effects, suggesting that underexpression of survival factors or overexpression of death-inducing factors accounted for the phenotypes observed. Tumor necrosis factor (TNF) levels were elevated in several tissues, especially thymus, suggesting that TNF may be a target gene for cux/CDP-mediated repression. These data suggest that cux/CDP regulates normal hematopoiesis, in part, by modulating the levels of survival and/or apoptosis factors expressed by the microenvironment. © 2001 by The American Society of Hematology.   CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: B. J. Wilson, R. Harada, L. LeDuy, M. D. Hollenberg, and A. Nepveu CUX1 Transcription Factor Is a Downstream Effector of the Proteinase-activated Receptor 2 (PAR2) J. Biol. Chem., January 2, 2009; 284(1): 36 - 45. 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	Copyright © 2001 by American Society of Hematology         Online ISSN: 1528-0020