INTRODUCTION AND EXPRESSION OF THE 400 KILOBASE PRECURSOR AMYLOID PROTEIN GENE IN TRANSGENIC MICE

Overexpression of the gene encoding the beta-amyloid precursor protein (APP) may have a key role in the pathogenesis of both Alzheimer's dis ease (AD) and Down Syndrome (DS). We have therefore introduced a 650 k ilobase (kb) yeast artificial chromosome (YAC) that contains the entir e, unrearranged 400 kb human APP gene into mouse embryonic stem (ES) c ells by lipid-mediated transfection. ES lines were generated that cont ain a stably integrated, unrearranged human APP gene. Moreover, we dem onstrate germ line transmission of the APP YAC in transgenic mice and expression of human APP mRNA and protein at levels comparable to endog enous APP. This transgenic strategy may prove invaluable for the devel opment of mouse models for AD and DS.