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US 2011/0035816 A1Published application
Genetically Modified Rat Models for Drug Metabolism
OwnerEric M. Ostertag, John Stuart Crawfordinventors
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OwnerEric M. Ostertag, John Stuart Crawfordinventors
Estimating the term…
The present invention provides a desired rat or a rat cell which contains a predefined, specific and desired alteration rendering the rat or rat cell predisposed to alterations in drug and chemical metabolism by modification of its structure or mechanism. Specifically, the invention pertains to a genetically altered rat, or a rat cell in culture, that is defective in at least one of two alleles of a drug metabolism gene such as the Cyp7b1 gene, the Cyp3a4 gene, etc. In another embodiment, the rat cell is a somatic cell. The inactivation of at least one drug metabolism allele results in an animal with a higher susceptibility to altered drug and chemical metabolism. In one embodiment, the genetically altered animal is a rat of this type and is able to serve as a useful model for altered drug and chemical metabolism or toxicology and as a test animal for autoimmune and other studies. The invention additionally pertains to the use of such rats or rat cells, and their progeny in research and medicine. In one embodiment, the invention provides a genetically modified or chimeric rat cell whose genome comprises two chromosomal alleles of a drug metabolism gene wherein at least one of the two alleles contains a mutation, or the progeny of the cell.
A genetically modified non-human mammal, or progenies thereof, at least some of whose cells comprise a genome comprising a genetic mutation in one or more genes that causes the mammal to have a greater susceptibility to drug and chemical metabolism or toxicology than a mammal not comprising the genetic mutation.
A genetically modified non-human mammal, or progenies thereof, whose genome is disrupted at one or more toxicology gene loci so as to produce a phenotype, relative to a wild-type phenotype, comprising abnormal altered drug metabolism function of the mammal.
A method for determining whether a compound is potentially useful for mediating drug transport, which includes (a) providing a cell that produces a drug transporter protein, (b) contacting the cell with the compound, and (c) monitoring the activity of the drug metabolism protein, such that a change in activity in response to the compound indicates that the compound is potentially useful for treating or alleviating the symptoms of a altered drug metabolism function.
A screening method for identifying useful compounds, comprising (a) providing an assay system comprising a rat model system comprising a genetically modified nonhuman mammal, or progenies thereof, at least some of whose cells comprise a genome comprising a genetic mutation in one or more toxicology genes that causes the mammal to have a greater susceptibility to chemoresistance or sensitivity than a mammal not comprising the genetic mutation;
A screening method for identifying useful compounds, comprising (a) providing an assay system comprising a model system comprising a genetically modified nonhuman mammal, or progenies thereof, at least some of whose cells comprise a genome comprising a genetic mutation in one or more toxicology gene that causes the mammal to have a greater susceptibility to chemoresistance or sensitivity induction than a mammal not comprising the genetic mutation;
Dependencies are inferred from the claim text.