New mouse model of Alzheimer's.
Amyloid β-peptide (Aβ) accumulation is a key characteristic of Alzheimer's disease (AD); therefore, mouse models of AD exhibiting Aβ pathology are valuable tools for unraveling disease mechanisms. However, the overexpression of Aβ precursor protein (APP) used in previous mouse models may cause Aβ-independent artifacts that influence data interpretation. To circumvent these problems, we used an APP knock-in (KI) strategy to introduce mutations to the mouse APP gene to develop a new generation of AD mouse models. These new models, termed APP(NL-F) and APP(NL-G-F), have endogenous APP levels and develop robust Aβ amyloidosis, which induce synaptic degeneration and memory impairments. Thus, we suggest that these novel APP KI mice will serve as important tools to elucidate molecular mechanisms of AD.
Laboratory for Proteolytic Neuroscience, RIKEN Brain Science Institute , 2-1 Hirosawa, Wako, Saitama 351-0198, Japan.
Per
P
Nilsson
Takashi
T
Saito
Takaomi C
TC
Saido
D000544:Alzheimer Disease / Q000473:pathology / Q000503:physiopathology; D016564:Amyloid beta-Protein Precursor / Q000235:genetics*; D000686:Amyloidosis / Q000473:pathology / Q000503:physiopathology; D000818:Animals; D001921:Brain / Q000473:pathology / Q000503:physiopathology; D002135:Calcium-Binding Proteins / Q000235:genetics / Q000378:metabolism; D004195:Disease Models, Animal; D055879:Gene Knock-In Techniques; D055786:Gene Knockout Techniques; D006801:Humans; D008569:Memory Disorders / Q000473:pathology / Q000503:physiopathology; D018345:Mice, Knockout; D008822:Mice, Transgenic; D009154:Mutation
D016564:Amyloid beta-Protein Precursor; D002135:Calcium-Binding Proteins; C033668:calpastatin