The Use of Genetically Modified Animals in Discovery Toxicology

Discovery Toxicology, Sctfety Assessment, Genentech, Inc., South San Francisco, CA, USA 

Drug Discovery Toxicology From Target Assessment to Translational Biomarkers, First Edition. Edited by Yvonne Will, J. Eric McDuffie, Andrew J. Olaharski, and Brandon D. Jeffy. 

Germ line KOs Rapid model generation Complete KO in all tissues Can be leveraged for developmental assessment Can be embryonic lethal Potential confounding developmental effects, which can over or underestimate toxicity Potential scaffolding effects can result in overestimation of toxicities 

Conditional KO in adulthood More relevant to pharmacological inhibition in adults Flexibility in timing of the KO Potential incomplete KO Limitations in obtaining KO in brain Potential confonnding effects of tamoxifen if nsed Potential scaffolding effects 

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