Tetracycline repressor regulated mammalian cell transcription and viral replication switch

A method for recombinantly producing a polypeptide in a mouse cell that makes the tet repressor protein, said method comprising:

• a) tranforming a mouse embryonic stem cell with a vector comprising:
• i) a mammalian promoter sequence having a TATA element;
• wherein said promoter is operable in adult mouse tissues.
• ii) at least one tet operator sequence positioned at least 6 nucleotides 3′ to the TATA element;
• and
• iii) a nucleic acid encoding said polypeptide lying 3′ to said tet operator and operably linked to said promoter;
• wherein said mouse embryonic stem cell comprises the tet repressor protein or is transformed with a vector that expresses the tet repressor protein;
• b) selecting a mouse embryonic stem cell that expresses said polypeptide;
• c) incorporating said mouse embryonic stem cell into a blastoyst to form a chimeric mouse embryo;
• d) implanting said chimeric mouse embryo into a pseudopregnant mouse;
• e) allowing said chimeric mouse embryo to develop into viable offspring;
• f) screening said viable offspring to identify heterozygous transgenic mice expressing said polypeptide;
• g) breeding said heterozygous transgenic mice to produce homozygous transgenic mice;
• and
• h) administering tetracycline to said homozygous transgenic mice to produce said polypeptide.