Mice transgenic for a tetracycline-controlled transcriptional activator

US5859310A · kind A · utility

Assignee

• BASF SE

Inventors

• Hermann Bujard · Heidelberg, DE
• Manfred Gossen · Corona, US
• Jochen G. Salfeld · North Grafton, US
• Jeffrey W. Voss · Holden, US

Key dates

• Filing date: Jun 7, 1995
• Grant date: Jan 12, 1999
• Expiry date: Jun 7, 2015

Classification

• Technology area (CPC C): Chemistry; Metallurgy
• CPC primary: C12N2830/006
• WIPO field: Biotechnology
• WIPO sector: Chemistry

Abstract

Transgenic mice carrying two transgenes, the first coding for a transactivator fusion protein comprising a tet repressor and a polypeptide which directly or indirectly activates transcription of a tet operator-linked gene in eucaryotic cells, and the second comprising a gene operably linked to a minimal promotor operably linked to at least one tet operator sequence, are disclosed. Isolated DNA molecules (e.g., targeting vectors) for integrating a polynucleotide sequence encoding a transactivator of the invention at a predetermined location within a second target DNA molecule by homologous recombination are also disclosed. Transgenic mice having the DNA molecules of the invention integrated at a predetermined location in a chromosome by homologous recombination are also encompassed by the invention. Methods to regulate the expression of a tet operator linked-gene of interest by administering tetracycline or a tetracycline analogue to a mouse of the invention are also disclosed. The regulatory system of the invention allows for conditional inactivation or modulation of expression of a gene of interest in a host cell or mouse.