An intrinsic but cell-nonautonomous defect in GATA-1-overexpressing mouse erythroid cells
| Autor: | Joost Gribnau, Frank Grosveld, M. F. T. R. De Bruijn, An Langeveld, Eric Milot, Rudolf W. Hendriks, Fokke Lindeboom, Alar Karis, Sjaak Philipsen, David Whyatt, Rita Ferreira |
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| Přispěvatelé: | Cell biology, Immunology |
| Rok vydání: | 2000 |
| Předmět: |
Male
Cell type X Chromosome Erythroblasts Cellular differentiation Transgene Cell Apoptosis Biology Animals Genetically Modified Mice Dosage Compensation Genetic medicine Animals Erythropoiesis GATA1 Transcription Factor Transcription factor Crosses Genetic Erythroid Precursor Cells Multidisciplinary Erythroid-Specific DNA-Binding Factors Chimera Anemia Molecular biology DNA-Binding Proteins Mice Inbred C57BL medicine.anatomical_structure Female Signal transduction Signal Transduction Transcription Factors |
| Zdroj: | Nature, 406, 519-524. Nature Publishing Group |
| ISSN: | 0028-0836 |
| Popis: | GATA-1 is a tissue-specific transcription factor that is essential for the production of red blood cells. Here we show that overexpression of GATA-1 in erythroid cells inhibits their differentiation, leading to a lethal anaemia. Using chromosome-X-inactivation of a GATA-1 transgene and chimaeric animals, we show that this defect is intrinsic to erythroid cells, but nevertheless cell nonautonomous. Usually, cell nonautonomy is thought to reflect aberrant gene function in cells other than those that exhibit the phenotype. On the basis of our data, we propose an alternative mechanism in which a signal originating from wild-type erythroid cells restores normal differentiation to cells overexpressing GATA-1 in vivo. The existence of such a signalling mechanism indicates that previous interpretations of cell-nonautonomous defects may be erroneous in some cases and may in fact assign gene function to incorrect cell types. |
| Databáze: | OpenAIRE |
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