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Epigenetic silencing and tissue independent expression of a novel tetracycline inducible system in double‐transgenic pigs
Author(s) -
Kues Wilfried A.,
Schwinzer Reinhard,
Wirth Dagmar,
Verhoeyen Els,
Lemme Erika,
Herrmann Doris,
Barg-Kues Brigitte,
Hauser Hansjörg,
Wonigeit Kurt,
Niemann Heiner
Publication year - 2006
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fj.05-5415fje
Subject(s) - transgene , transgenesis , expression cassette , biology , epigenetics , gene silencing , tetracycline , gene expression , gene , genetics , microbiology and biotechnology , computational biology , vector (molecular biology) , recombinant dna , reproductive technology , embryogenesis , antibiotics
The applicability of tightly regulated transgenesis in domesticated animals is severely hampered by the present lack of knowledge of regulatory mechanisms and the long generation intervals. To capitalize on the tightly controlled expression of mammalian genes made possible by using prokaryotic control elements, we have used a single-step transduction to introduce an autoregulative tetracycline-responsive bicistronic expression cassette (NTA) into transgenic pigs. Transgenic pigs carrying one NTA cassette showed a mosaic transgene expression restricted to single muscle fibers. In contrast, crossbred animals carrying two NTA cassettes with different transgenes, revealed a broad tissue-independent and tightly regulated expression of one cassette, but not of the other one. The expression pattern correlated inversely with the methylation status of the NTA transcription start sites indicating epigenetic silencing of one NTA cassette. This first approach on tetracycline regulated transgene expression in farm animals will be valuable for developing precisely controlled expression systems for transgenes in large animals relevant for biomedical and agricultural biotechnology.