Disruption of PLZP in mice leads to increased T-lymphocyte proliferation, cytokine production, and altered hematopoietic stem cell homeostasis Journal Article
| Authors: | Piazza, F.; Costoya, J. A.; Merghoub, T.; Hobbs, R. M.; Pandolfi, P. P. |
| Article Title: | Disruption of PLZP in mice leads to increased T-lymphocyte proliferation, cytokine production, and altered hematopoietic stem cell homeostasis |
| Abstract: | Deregulated function of members of the POK (POZ and Krüppel) family of transcriptional repressors, such as promyelocytic leukemia zinc finger (PLZF) and B-cell lymphoma 6 (BCL-6), plays a critical role in the pathogenesis of acute promyelocytic leukemia (APL) and non-Hodgkin's lymphoma, respectively. PLZP, also known as TZFP, FAZF, or ROG, is a novel POK protein that displays strong homology with PLZF and has been implicated in the pathogenesis of the cancer-predisposing syndrome, Fanconi's anemia, and of APL, in view of its ability to heterodimerize with the FANC-C and PLZF proteins, respectively. Here we report the generation and characterization of mice in which we have specifically inactivated the PLZP gene through in-frame insertion of a lacZ reporter and without perturbing the expression of the neighboring MLL2 gene. We show that PLZP-deficieet mice display defects in cell cycle control and cytokine production in the T-cell compartment. Importantly, PLZP inactivation perturbs the homeostasis of the hematopoietic stem and/or progenitor cell. On the basis of our data, a deregulation of PLZP function in Fanconi's anemia and APL may affect the biology of the hematopoietic stem cell, in turn contributing to the pathogenesis of these disorders. |
| Keywords: | immunohistochemistry; controlled study; protein expression; unclassified drug; gene deletion; nonhuman; flow cytometry; cell proliferation; t lymphocyte; antigens, cd3; cd8-positive t-lymphocytes; t-lymphocytes; animal cell; mouse; animals; mice; mice, knockout; animal tissue; dna damage; gene; gene targeting; cell cycle; gene expression; animal experiment; mice, mutant strains; protein; genotype; animalia; cytokines; amino acid sequence; molecular sequence data; reverse transcriptase polymerase chain reaction; gene disruption; cd4-positive t-lymphocytes; hematopoietic stem cells; beta galactosidase; cytokine production; models, genetic; genes, reporter; hematopoietic stem cell; gene insertion; homeostasis; blotting, northern; repressor proteins; cell separation; testis; mutagenesis; transgenes; ribonucleases; fanconi anemia; testis development; lac operon; mll2 gene; male; priority journal; article; protein plzp; insertion sequences |
| Journal Title: | Molecular and Cellular Biology |
| Volume: | 24 |
| Issue: | 23 |
| ISSN: | 0270-7306 |
| Publisher: | American Society for Microbiology |
| Date Published: | 2004-12-01 |
| Start Page: | 10456 |
| End Page: | 10469 |
| Language: | English |
| DOI: | 10.1128/mcb.24.23.10456-10469.2004 |
| PROVIDER: | scopus |
| PMCID: | PMC529048 |
| PUBMED: | 15542853 |
| DOI/URL: | |
| Notes: | Mol. Cell. Biol. -- Cited By (since 1996):30 -- Export Date: 16 June 2014 -- CODEN: MCEBD -- Source: Scopus |
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