Transgenic studies models

In a Tg.AC transgenic mouse model using similar doses to the first mouse study, there was no treatment-related increase in the incidence of skin tumours after skin application. 

LA-ICP-MS has been developed for the detection and imaging of (3-amyloid protein in immuno-histochemical sections from the brain of a transgenic mouse model of Alzheimer s disease. The distribution of (3-amyloid deposits in tissue based on measurements of Eu and Ni coupled antibodies has been studied by McLeods group.170... 

The chemotaxis of mononuclear leukocytes and the migration, growth, and activation of the multiple cell types within atherosclerotic lesions are critical for the chronic inflammatory and fibroproliferative response in atherosclerosis (Ml). Chemokine-mediated attraction of leukocytes to tissues has been shown in atherosclerotic lesions (G8). Studies using knockout and transgenic murine models indicated that chemokine receptor/ligand interactions are crucial in the development of atherosclerosis (P6). Moreover, chemokines may also interfere with smooth muscle cell migration and growth, and platelet activation and other well-defined features of the atherosclerotic process (A2). 

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. 

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