Transgenic non-human animals for pharmacological and toxicological studies
AssigneeGene Stream Pty Ltd.
InventorJohn Michael Daly
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Abstract
The present invention is directed to the production, breeding and use of transgenic non-human animals such as mice in which specific genes or portions of genes have been replaced by homologues from another animal to make the physiology of the animals so modified more like that of the other animal with respect to drug pharmacokinetics and metabolism. The invention also extends to the use of the genetically modified non-human animals of the invention for pharmacological and/or toxicological studies.
Claims17
A method of predicting a behavior of a single drug or a plurality of drugs in a human, as part of a drug screening or evaluation process, comprising
- administering the single drug or the plurality of drugs to a transgenic mouse comprising in its genome a homozygous disruption of an endogenous mouse multidrug-resistance-associated protein (MRP) gene and a stably integrated nucleotide sequence that encodes a human MRP polypeptide operably linked to a promoter selected from the group consisting of an endogenous mouse MRP gene promoter, and the human MRP gene promoter, wherein the human MRP polypeptide is a homologue of the endogenous mouse MRP, wherein the expression of the endogenous MRP gene is abrogated, and wherein expression of the nucleotide sequence that encodes the human MRP polypeptide provides a mouse that predicts behavior of a drug in a human, and
- conducting analytical tests to determine the behavior of the single drug or the plurality of drugs in the transgenic mouse, the results of which have a higher correlation to the behavior of the drug in the human than the results obtained from a wild type mouse.
Dependencies are inferred from the claim text.