Animals transgenic for a tetracycline-regulated transcriptional inhibitor
OwnerHermann Bujard, Manfred Gosseninventors
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OwnerHermann Bujard, Manfred Gosseninventors
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Transgenic animals carrying a transgene comprising a nucleic acid molecule encoding protein useful for regulating the expression of genes in eukaryotic cells and organisms in a highly controlled manner are disclosed. In the regulatory system of the invention, transcription of a tet operator-linked nucleotide sequence is inhibited by a transcriptional inhibitor fuision protein composed of two polypeptides, a first polypeptide which binds to tet operator sequences and a second polypeptide which directly or indirectly inhibits transcription in eukaryotic cells. In various embodiment, the first polypeptide binds to tet operator sequences either: (i) in the absence but not the presence of tetracycline (or an analogue thereof) or (ii) in the presence but not the absence of tetracycline (or an analogue thereof). In a preferred embodiment, the transgene encoding the transcriptional inhibitor fusion protein is integrated at a predetermined location within the chromosome of the transgenic animal.
A non-human transgenic animal having a transgene comprising a polyncleotide sequence encoding a fusion protein which inhibits transcription in eukaryotic cells, the fusion protein comprising a first polypeptide which binds to a tet operator sequence, operatively linked to a heterologous second polypeptide which inhibits transcription in eukaryotic cells.
A non-human transgenic animal having a transgene comprising a polynucleotide sequence encoding a fusion protein which inhibits transcription in eukaryotic cells, the fusion protein comprising a first polypeptide which binds to a tet operator sequence, operatively linked to a heterologous second polypeptide which inhibits transcription in eukaryotic cells, wherein the transgene is integrated by at a predetermined location within a chromosome within cells of the animal.
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