P1–010: Apolipoprotein E isoform–specific modulation of innate immune response neurotoxicity in a targeted replacement APOE mouse model

iii) whether deficiency of any of these fragments underlies the lethal phenotypes of APP/APLP knockout mutants. Methods: To address these issues we have generated knockin (KI) mice expressing APP-deletion mutants under control of the endogenous APP promoter. Results: APPs -KI mice carry a stop codon behind the -secretase site and thus express solely the secreted APPs ectodomain. APP CT15-KI mice lack the last 15 amino acids of APP harboring the YENPTY protein interaction motif. Current work is aimed at analyzing whether these APP-KI mutants can reverse the phenotype of APP-deficient mice and at assessing the role of C-terminal interactions for in vivo processing of APP. Conclusions: Phenotypic analysis of these mouse mutants should allow us to delineate essential functional domains of APP-family proteins.