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P1–010: Apolipoprotein E isoform–specific modulation of innate immune response neurotoxicity in a targeted replacement APOE mouse model
Author(s) -
Montine Kathleen S.,
Maezawa Izumi,
Nivison Mary,
Maeda Nobuyo,
Montine Thomas J.
Publication year - 2006
Publication title -
alzheimer's and dementia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 6.713
H-Index - 118
eISSN - 1552-5279
pISSN - 1552-5260
DOI - 10.1016/j.jalz.2006.05.385
Subject(s) - neurotoxicity , apolipoprotein e , microglia , biology , innate immune system , immunology , immune system , medicine , inflammation , toxicity , disease
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.