METHOD FOR PRODUCING TRANSGENIC ANIMAL MODELS WITH MODULATED PHENOTYPE AND ANIMALS PRODUCED THEREFROM

摘要

A method of preparing a transgenic animal model with enhanced, accelerated pathology for Alzheimer's Disease (AD) and the transgenic animal made by the method are disclosed. The method includes producing an F1 generation by crossing a first and second transgenic parent each carrying a different expressible transgene for differing aspects of the same desired phenotype associated with AD pathology. The offsprings of the F1 generation are then screened and those which carry a transgene from each parental transgenic animal resulting in an enhanced pathology for Alzheimer's Disease are selected. In a preferred embodiment the AD-associated pathology is for amyloid accumulation. In an embodiment a mutant presenilin transgene and a transgene for a mutant amyloid precursor protein are used. In a further embodiment the mutant presenilin transgene is the PS1 M146L mutation and the mutant amyloid precursor protein transgene is the Swedish mutation (app695 isoform containing a K670N, M671L mutation (app770 numbering )).