Transgenes encoding mutant simian virus 40 large T antigens unmask phenotypic and functional constraints in thymic epithelial cells
| Autor: | Moll J, Eibel H, Botteri F, Sansig G, Catherine Regnier, van der Putten H |
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Antigens
Polyomavirus Transforming Macrophage Colony-Stimulating Factor Temperature Cell Differentiation Epithelial Cells Simian virus 40 Thymus Gland Growth Hormone-Releasing Hormone Receptors Interleukin-4 Mice Inbred C57BL Mice Proto-Oncogene Proteins c-kit Phenotype Proto-Oncogene Proteins Receptors Mitogen Mutation Animals Interleukin-4 |
| Zdroj: | Europe PubMed Central |
| Popis: | Transgenes encoding simian virus 40 (SV40) T antigen (Tag) can cause hyperplastic or tumorigenic lesions of desired but also of unforeseen cellular origin. Unexpectedly the human growth hormone-releasing factor (GRF) gene promoter directs expression of SV40 Tag specifically in thymic epithelial (TE) cells. Expression starts in the neonate, in which GRF-Tag+ cells display strict numerical and spatial constraints. Tag supersedes mechanisms that constrain these features and GRF-Tag mice develop thymic hyperplasia. To characterize GRF-Tag+ TE cells and their putative normal counterparts we compared phenotypic and functional effects caused by transgenes encoding mutant large T antigens. This strategy is applicable to any situation in which T antigen is used to alter development. One large Tag mutant (K1 + 5080) does not cause thymic hyperplasia. GRF-Tag (K1 + 5080)+ TE cells display strict temporal and spatial constraints throughout life. TE cells expressing other mutant large T antigens that cause thymic hyperplasia do not obey these rules and reveal that phenotypically distinct GRF-Tag+ TE-cell stages exist in vivo. Analysis of conditional immortal GRF-Tag(tsA58)+ TE cells expressing a temperature-sensitive large Tag shows that large Tag blocks differentiation in these cells. Phenotype and functions in these cells are regulated by cellular differentiation and interleukin 4 (IL-4). |
| Databáze: | OpenAIRE |
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