Abstract
To differentiate multiple activities of presenilin 1 (PS1), we generated transgenic mice expressing two human PS1 alleles: one with the aspartate to alanine mutation at residue 257 (hPS1D257A) that impairs the proteolytic activity of PS1, and the other deleting amino acids 340-371 of the hydrophilic loop sequence (hPS1Δcat) essential for β-catenin interaction. We show here that although hPS1Δcat is fully competent in rescuing the PS1-null lethal phenotype, hPS1D257A does not exhibit developmental activity. hPS1D257A also leads to the concurrent loss of the proteolytic processing of Notch and β-amyloid precursor protein (APP) and the generation of β-amyloid peptides (Aβ). Further, by measuring the levels of endogenous AβX-40 and AβX-42 in primary neuronal cultures, we confirmed the concept that PS1 is indispensable for the production of secreted Aβ.
Original language | English (US) |
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Pages (from-to) | 8760-8765 |
Number of pages | 6 |
Journal | Proceedings of the National Academy of Sciences of the United States of America |
Volume | 99 |
Issue number | 13 |
DOIs | |
State | Published - Jun 25 2002 |
ASJC Scopus subject areas
- General