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AssigneeTularik Inc.
InventorsBei Shan, R. Marc Learned, M. Catherine Amaral, Steven L. McKnight, Fabienne Charles de la Brousse, Jin-Long Chen
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The invention provides methods and compositions for screening for pharmacological agents which regulate gene expression in mammals. An exemplary assay involves (a) contacting a mammalian cell comprising a knock-in mutant of a targeted native allele encoding a reporter of gene expression, wherein the expression of the reporter is under the control of the gene expression regulatory sequences of the native allele, with a candidate agent under conditions whereby but for the presence of the agent, the reporter is expressed at a first expression level; and, (b) measuring the expression of the reporter to obtain a second expression level, wherein a difference between the first and second expression levels indicates that the candidate agent modulates gene expression.
An isolated genetic knock-in cell, wherein said cell is, or is a progeny of, a genetic knock-in primary cell obtained from a transgenic mouse made by homologous recombination of a targeted native allele with a transgene comprising a sequence encoding a reporter flanked by flanking sequences which effect the homologous recombination of said transgene with said native allele, wherein the expression of said reporter is under the control of native gene expression regulatory sequences of said native allele, and said native allele is selected from the group consisting of a human cholesterol 7-α hydroxylase allele, a mouse ob (leptin) allele, a human LDL receptor allele, a human TNFα allele, a human E-selectin allele, a human UCP-2 allele, a mouse UCP-2 allele, a mouse Ob receptor allele, a human ∈ (epsilon) allele, a mouse STAT6 allele, a human EPAS-1 allele, a human utrophin allele, and an African green monkey HNF-1α allele.
A cell-based method for screening for modulators of a targeted gene expression, said method comprising steps:
Dependencies are inferred from the claim text.