GENETIC-MODIFICATION OF THE PHENOTYPES PRODUCED BY AMYLOID PRECURSOR PROTEIN OVEREXPRESSION IN TRANSGENIC MICE

Overexpression of Alzheimer amyloid precursor protein (APP) produces d ramatically different phenotypes in transgenic mice depending on the g enetic background, For example, concentrations of APP that produce amy loid plagues in outbred transgenic lines are lethal for inbred FVB/N o r C57BL/6J mice, Expression of SOD1 transgenes is protective, suggesti ng involvement of oxidative damage in premature death, but ablation of Apoe had no significant effect, In contrast, FGF2 transgene overexpre ssion enhances the lethal effects of APP. Differential survival does n ot appear to reflect genetic differences in APP processing, but rather host responses to APP or its derivatives.