Transgenic animal models development

The use of nonrelevant animal species is discouraged as the results of such studies may be misleading (per ICH S6). Therefore the next option, when available, is to substitute a relevant transgenic animal model for a pharmacologically relevant species. Transgenic animal models for human EpCAM have been developed, but they either have a different tissue expression pattern from that seen in humans [41,43] or the model has not been validated [40], making them unsuitable for the evaluation of the safety of anti-EpCAM immunotherapeutics. 

The discovery of the isoprostanes, recent studies performed in living patients (PraticO et al. 2000), and the development of transgenic animal models of Alzheimer s disease amyloidosis are three important factors helping us to understand and define the role that reactive oxygen species might play in the pathogenesis of this disease (for review see Pra-tic6 2002). 

The clinical consequences of the currently used benzodiazepines range from sedation, muscle relaxation, seizure reduction, anxiolysis, and hypnosis. Clearly, it would be highly desirable to be able to separate some of these effects. In addition, it would be useful to reduce other undesirable consequences such as development of tolerance and dependence, abuse, synergistic interaction with ethanol, and memory impairment (for a comprehensive review see [22]). Animal models for some of the aforementioned conditions, in combination with transgenic mouse technology, have recently led to a deeper understanding of the contribution some of the individual a subunits make to these behaviors. 

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