Spatial and temporal down-regulation of transgene expression using the TRSID-silencer in mice: Application to Prnp

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 Pr...

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Bibliographic Details
Published in:FEBS letters 2008-06, Vol.582 (15), p.2219-2224
Main 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
Format: Article
Language:English
Subjects:
Animals
Cellular Biology
cellular prion protein
chimeric tetracycline repressor that recruits histone deacetylases
Down-Regulation
Gene Expression
Gene regulation
Inducible promoter
Life Sciences
Mice
Mice, Transgenic
Neurons - metabolism
Prion
PrPC
PrPC Proteins - genetics
PrPSc
scrapie-associated PrP
Sheep - genetics
Silencer Elements, Transcriptional
tetracycline trans-activator
Transgenes
Transgenic mice
transmissible spongiform encephalopathies
TRSID
TSE
tTA
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Summary: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.
ISSN:0014-5793
1873-3468
DOI:10.1016/j.febslet.2008.05.014