Genetically modified animal models

CPMP/SWP/2592 /04 Revl. Conclusions and recommendations on the use of genetically modified animal models for carcinogenicity assessment. 2004. 

USE OF GENETICALLY MODIFIED ANIMAL MODELS IN DISCOVERY TOXICOLOGY... 

Genetically modified animals serve as disease models for human diseases. 

While most strains respond consistently to this paradigm due to its independence from motor activity, specific mouse strains (e.g., FVB/N) have considerably higher baseline body temperatures and should be avoided in this model (21). However, this procedure has been shown to effectively induce hyperthermia to varying degrees in all inbred and outbred strains tested (41) and is also an effective indicator of stress in genetically modified animals (34). 

MODIFICATIONS OF THE METHOD Animal models with spontaneous disease exist and can be used in place of the toxicant-induced models. In addition, an investigator may take advantage of either genetically-modified animals or exploit strain differences in sensitivity to xenobiotics to examine mechanisms of renal injury. 

It has become accepted that the main pharmaceutical areas where metabonomics is impacting include validation of animal models of disease, including genetically modified animals preclinical evaluation of drug safety studies allowing ranking of candidate compounds assessment of safety in humans in clinical trials after product launch, quantitation, or ranking of the beneficial effects of pharmaceuticals. 

In addition to the role of genetically modified animals in target safety assessment and investigating mechanisms of toxicity, a key use of these animal models is the assessment of drug metabolism and toxicokinetics of experimental therapeutics, with drug exposure playing an important role in overall safety. The properties of absorption, disuibntion, metabolism, and elimination (ADME) for small-molecnle... 

Recio L and Everitt J (2001) Use of genetically modified mouse models for evaluation of carcinogenic risk Consideration for the laboratory animal scientist. Comparative Medicine 51 399—405. 

In the case of spontaneous autoimmune diseases mice are the most frequently used animal model. With the advent of transgenic and genetically modified (knockout, KO) mice, the number of genetically predisposed autoimmune models has substantially increased. Other species that have been useful include rats, monkeys, cats, dogs, rabbits, and chickens for some specific forms of autoimmune diseases [4, 5]. 

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