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• W207312225 startingPage "151" @default.
• W207312225 abstract "Genetically engineered (GE) animals (mainly mice, GEM, or rats, GER) that either over-express a foreign gene (transgenic) or in which the activity of a gene has been removed (‘knockout’), replaced (‘knockin’), or temporarily repressed (‘knockdown’) are being utilized increasingly in both the biopharmaceutical and pharmaceutical industries to explore mechanisms of disease, to evaluate new therapeutic targets, and to screen drug candidates for efficacy and/or potential toxicity. Recent innovations in genetic engineering technology of relevance to drug discovery and development (DDD) programs include the construction of animals with (1) multiple engineered genes, (2) or mutations that can be activated at particular sites and/or times, (3) or with a human gene inserted in place of its animal counterpart (‘humanized’ animals), and (4) the ability to execute such procedures in a high-throughput fashion. The goals of phenotypic analysis are to fully discern the physiological alterations (phenotype) induced by the engineered gene (genotype), and if feasible to define one or more easily measured biomarkers that can be used to monitor the progress of disease and the impact of therapeutic intervention on the engineered condition. Ideally in DDD the biomarkers for the engineered model also can be adapted for use in human patients. Many caveats must be considered when interpreting data derived from GEM or GER during DDD, the primary of which will be (1) the extent to which each rodent's unique genotype controls its phenotype, (2) the degree to which a model's reproducible phenotype has been defined, and (3) the possibility of misconstruing the presence or absence of a phenotype due to either compensatory processes that mask the functional effects produced by the engineered gene or the use of an insufficiently sensitive battery of tests during phenotypic analysis. In current DDD practice, information acquired using GEM or GER models supplements the data gained using bioassays conducted with wild-type (normal) animals. However, given the accelerated onset of disease in engineered animals relative to the heterogeneous genetic make-up of human and wild-type rodent populations, more GEM and GER models will be used in the future as ‘gold standard’ models to increase the pace of DDD." @default.
• W207312225 created "2016-06-24" @default.
• W207312225 creator A5011929463 @default.
• W207312225 date "2007-01-01" @default.
• W207312225 modified "2023-09-23" @default.
• W207312225 title "Genetically Engineered Animals" @default.
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