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Cell-type specific and regulated transgene expression from first generation recombinant adenoviral vectors: Characterisation in vitro and in vivo
Başlık:
Cell-type specific and regulated transgene expression from first generation recombinant adenoviral vectors: Characterisation in vitro and in vivo
Yazar:
Smith-Arica, Joseph, author.
ISBN:
9780438043503
Yazar Ek Girişi:
Fiziksel Tanımlama:
1 electronic resource (195 pages)
Genel Not:
Source: Dissertation Abstracts International, Volume: 76-08C.
Özet:
We have developed combined cell-type specific and inducible vectors for transgene expression in the brain and pituitary in vitro and in vivo. To achieve cell-type specific transcriptional targeting combined with inducible expression, we have driven the expression of the tetracycline-dependent transcriptional elements by the astrocyte specific, glial fibrillary acidic protein (GFAP), neuronal specific, neuronal specific enolase (NSE), or an anterior pituitary, lactotroph specific, prolactin (PRL) promoter elements, within a dual adenoviral vector system. Cell-type specificity, inducibility, and strength of expression were characterised in vitro in cell lines, and in primary cultures of brain and pituitary, and in vivo, and compared to a powerful pancellular ?-actin/ human cytomegalovirus (hCMV) promoter. We demonstrate that the GFAP promoter is able to restrict tetracycline-dependent transgene expression to glial cells in cell lines, primary cultures, and in vivo in the hippocampus, while the PRL promoter behaves in a similar way but its expression is restricted to lactotrophic cell lines, anterior pituitary lactotrophs in cultures, and pituitary lactotrophs in the pituitary in vivo. However, the NSE promoter did not show neuronal restricted transgene expression in vitro, but did so in vivo. Our dual viral system also has provided evidence that an excess of transactivator is needed to achieve maximal expression with weaker cell-type specific promoters. Transgene expression could be completely shut-off in the presence of doxycycline, both in vitro and in vivo. Consequently, our strategy demonstrates for the first time that combined cell-type specificity and simultaneous regulation of transgene expression can be obtained in the brain and pituitary using adenoviral vectors.
Notlar:
School code: 1543
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Yer Numarası | Demirbaş Numarası | Shelf Location | Lokasyon / Statüsü / İade Tarihi |
---|---|---|---|
XX(684287.1) | 684287-1001 | Proquest E-Tez Koleksiyonu | Arıyor... |
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