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

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.

Abbreviations: TSE, transmissible spongiform encephalopathies, tTA, tetracycline trans-activator, TRSID, chimeric tetracycline repressor that recruits histone deacetylases, PrP^C, cellular prion protein, PrP^Sc, scrapie-associated PrP

Keywords: Inducible promoter, Transgenic mice, Prion, Gene regulation