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The use of animal models in expression pharmacogenomic analyses

The Pharmacogenomics Journal volume 1, pages 48–58 (2001)Cite this article

Abstract

Expression pharmacogenomics applies genome/proteome scale differential expression technologies to both in vivo and in vitro models of drug response to identify candidate markers correlative with and predictive of drug toxicity and efficacy. It is anticipated to streamline drug development by triaging towards lead compounds and clinical candidates that maximize efficacy while minimizing safety risks. As the majority of expression pharmacogenomics will be performed on preclinical therapeutic candidates, compatibility with favored preclinical animal model systems will be essential. This review will address expression pharmacogenomics in the context of those animal model systems commonly used for pharmacokinetic, pharmacodynamic and toxicologic analyses. Specific discussions will cover: (A) relative robustness of genomic and proteomic technology platforms used to generate drug response data in critical model systems; (B) animal handling, treatment and other experimental design optimizations; (C) data analysis strategies for extracting and validating candidate pharmacogenomic markers; and (D) overarching limitations in applying expression pharmacogenomics to animal model systems.

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Abbreviations

DGE:

differential gene expression

UTHS:

ultra-high-throughput screening

IND:

investigational new drug

RYQ-PCR:

real-time quantitative polymerase chain reaction

EST:

expressed sequence tag

DD:

differential display

SAGE:

serial analysis of gene expression

RDA:

representational difference analysis

TOGA:

total gene expression analysis

2DE:

two-dimensional gene electrophoresis

SSRI:

selective serotonin uptake inhibitor

ANOVA:

analysis of variance

PCA:

principle components analysis

GO:

gene ontology

SHR:

spontaneously hypertensive

WKY:

Wistar-Kyoto

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  1. CuraGen Corporation, New Haven, CT, USA

    B E Gould Rothberg

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  1. B E Gould Rothberg
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Correspondence to B E Gould Rothberg.

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Rothberg, B. The use of animal models in expression pharmacogenomic analyses. Pharmacogenomics J 1, 48–58 (2001). https://doi.org/10.1038/sj.tpj.6500008

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