Animals transgenic for a tetracycline-regulated transcriptional inhibitor

US5866755A · kind A · utility

Assignees

• BASF SE
• Knoll, Inc. · DE

Inventors

• Hermann Bujard · Heidelberg, DE
• Manfred Gossen · Corona, US

Key dates

• Filing date: Jun 7, 1995
• Grant date: Feb 2, 1999
• Expiry date: Jun 7, 2015

Classification

• Technology area (CPC C): Chemistry; Metallurgy
• CPC primary: C12N2830/32
• WIPO field: Pharmaceuticals
• WIPO sector: Chemistry

Abstract

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 fusion 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.