Patent ID: 6114599
Filing Date: 2000-09-05
Classification: A01K,A61K,A61P,C07K,C12N

Abstract:
A method for producing a recombinant, glucose-regulated insulin-producing beta cell whose proliferation is controlled by tetracycline or a derivative thereof, comprising the steps of:(a) introducing into the genome of a first mouse a first nucleic acid comprising a DNA molecule encoding a tetracycline responsive transcriptional activator operatively linked to an insulin promoter, wherein said tetracycline responsive transcriptional activator is expressed in the beta cells of said first mouse, thereby generating a first genetically modified mouse;(b) introducing into the genome of a second mouse a second nucleic acid comprising a DNA molecule encoding SV40 T antigen operatively linked to a tetracycline operator minimal promoter, thereby generating a second genetically modified mouse;(c) crossing said first genetically modified mouse or offspring thereof with said second genetically modified mouse or offspring thereof, to obtain progeny of said first and second genetically modified mice;(d) screening said progeny for doubly transgenic mice that bear a beta cell tumor wherein said tetracycline responsive transcriptional activator acts upon the tetracycline operator minimal promoter such that beta cell proliferation is controlled by tetracycline or a derivative thereof; and(e) isolating a recombinant, glucose-regulated insulin-producing beta cell whose proliferation is controlled by tetracycline or a derivative thereof, and wherein said beta cell is glucose regulated in the range of 5-15 mM.