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Spatial and temporal down-regulation of transgene expression using the TRSID-silencer in mice: application to Prnp |
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| Authors: | Gallozzi Micaela Béringue Vincent Decaunes Pauline Le Dur Annick Le Roux Karine Tilly Gaëlle Le Guillou Sandrine Herzog Laetitia Peyre Coralie Ladroue Aline Chapuis Jérôme Vilotte Marthe Passet Bruno Costa José Chenais Nathalie Le Provost Fabienne Laude Hubert Vilotte Jean-Luc |
| Institution: | Laboratoire de Génétique Biochimique et de Cytogénétique, Institut National de la Recherche Agronomique, 78350 Jouy-en-Josas, France. |
| Abstract: | Spatial and temporal control of ovine prion protein (Prnp) gene expression was achieved in mice using two transgenes: a Prnp minigene with tet-operator sequences inserted 5' to exon 1 and a mouse neurofilament genomic clone carrying the chimeric-repressor TRSID cDNA. In bi-transgenic mice, ovine PrP(C) expression could be reversibly controlled in neuronal cells by doxycycline treatment whereas it remains constant in other cell types. Overall, this model opens opportunities to assess the involvement of cell types in prion diseases and PrP physiological function. It demonstrates the potentiality of the TRSID-silencer to precisely control temporal and spatial gene expression in vivo. |
| Keywords: | TSE transmissible spongiform encephalopathies tTA tetracycline trans-activator TRSID chimeric tetracycline repressor that recruits histone deacetylases PrPC cellular prion protein PrPSc scrapie-associated PrP |
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