Transgenic animal models in toxicology: historical perspectives and future outlook.

  title={Transgenic animal models in toxicology: historical perspectives and future outlook.},
  author={D. R. Boverhof and Mark Chamberlain and Clifford R. Elcombe and Frank J. Gonzalez and Robert H Heflich and Lya G. Hern{\'a}ndez and Abigail C Jacobs and David Jacobson-Kram and Mirjam Luijten and Adriana Maggi and Mugimane G. Manjanatha and Jan van Benthem and B. Bhaskar Gollapudi},
  journal={Toxicological sciences : an official journal of the Society of Toxicology},
  volume={121 2},
Transgenic animal models are powerful tools for developing a more detailed understanding on the roles of specific genes in biological pathways and systems. Applications of these models have been made within the field of toxicology, most notably for the screening of mutagenic and carcinogenic potential and for the characterization of toxic mechanisms of action. It has long been a goal of research toxicologists to use the data from these models to refine hazard identification and characterization… 

Figures and Tables from this paper

Modeling Genetic Susceptibility to Disease☆
New and Emerging Genetic Toxicity Tests and Approaches to Genetic Toxicology Testing
An established test, the transgenic rodent (TGR) gene mutation assay, is presented as a test whose use for regulatory decision-making may increase due to the recent introduction of robust testing protocols and new test guidelines.
Mutation as a Toxicological Endpoint for Regulatory Decision‐Making
In vitro and in vivo somatic cell mutation data are most commonly used by regulatory agencies for hazard identification, that is, determining whether or not a substance is a potential mutagen and carcinogen, quantitative mutagenicity dose–response data are being used increasingly for risk assessments.
Applications and considerations for the use of genetically engineered mouse models in drug development
Considering high drug attrition rates in clinical studies and the overall complexity and challenging environment of drug development, it is increasingly important to understand the therapeutic
Transgenic mice and metabolomics for study of hepatic xenobiotic metabolism and toxicity
With genetically modified mouse models, metabolomics can determine the metabolic map of many xenobiotics with a level of sensitivity that allows the discovery of even minor metabolites, and this technology can be used for determining the mechanism of xenobiotic toxicity and to find early biomarkers for toxicity.
Improving prediction of carcinogenicity to reduce, refine, and replace the use of experimental animals.
A weight-of-evidence evaluation based on short-term toxicologic, in silico, and pharmacologic data is a promising approach to identify with reasonable certainty those pharmaceuticals that present a likely cancer risk in humans and, conversely, those that do not present a human cancer risk.


Review Article: Use of Transgenic Animals for Carcinogenicity Testing: Considerations and Implications for Risk Assessment
Before transgenic and knockout mice can be used as an adjunct or alternative to the conventional 2-year rodent bioassay, information related to the animal line to be used, study design, and data analysis and interpretation must be carefully considered.
Alternative Models for Carcinogenicity Testing: Weight of Evidence Evaluations Across Models
  • S. Cohen
  • Biology
    Toxicologic pathology
  • 2001
Comparison of the results between the various in vivo models suggest that they might have usefulness as screening bioassays for hazard identification for potential human carcinogens, and they have the benefits of being quicker, less expensive, and involve fewer animals than the traditional 2-year mouse bioassay.
The transgenic mouse assay as an alternative test method for regulatory carcinogenicity studies--implications for REACH.
Prospects for safety testing: A strategy for the application of transgenic rodent mutagenesis assays
The unique niche that transgenic mutagenesis systems can fill in product development and registration strategies is described, including follow up mutagenic effects demonstrated in Salmonella, Escherichia coli, mouse lymphoma, or other in vitro systems.
Zebrafish embryos as models for embryotoxic and teratological effects of chemicals.
Transgenic models in xenobiotic metabolism and toxicology.
Detailed review of transgenic rodent mutation assays.
Techniques: reporter mice - a new way to look at drug action.
Novel transgenic rat for in vivo genotoxicity assays using 6‐thioguanine and Spi− selection
This novel transgenic rat could be useful for investigating species differences between rats and mice in their response to genotoxic agents and for investigating in vivo mutagenicity assays.
Background and Framework for ILSI's Collaborative Evaluation Program on Alternative Models for Carcinogenicity Assessment
A large-scale collaborative research program to help to better characterize the responsiveness of several models proposed for use in carcinogenicity assessment and the database from these studies represents an important contribution to the future application of new models for human cancer risk assessment.