Studying Physiological Functions of APP Using Mice Models



Journal Title

Journal ISSN

Volume Title



Beta-amyloid precursor protein (APP) is sequentially cleaved by alpha /beta - secrease and gamma-secrease into three pieces: a soluble ectodomain (sAPPalpha or sAPPbeta ), a p3 or Abeta peptide, and an APP intracellular domain (AICD). Mounting evidence indicates the neuroprotective and neurotrophic effects of sAPP domain. In order to find out whether sAPP domain carries out the major physiological function of APP, we have generated knock-in mice that express truncated ectodomain of APP at beta-cleavage site (sAPPbeta ) with FLAG tag at C-terminus. The knock-in mice were viable and fertile, with no obvious phenotype. However, when sAPPbeta - FLAG knock-in mice were bred to APLP2 knockout background ("knockin/ knockout" mice), the expression of sAPPbeta -FLAG failed to fully rescue the postnatal lethal phenotype of APP/APLP2 double knockout pups, suggesting sAPPbeta alone cannot substitute for the function of full length APP. We quantified the expression levels of a series of synaptic proteins and AICD-interacting proteins in the brains of new born APP/APLP2 double knockout (DKO) pubs, as well as in the "knock-in/knockout" (KI/KO) pubs, and found that Fe65 protein expression level is upregulated in brains from DKO pubs but not the KI/KO pubs. Collaborating with Dr. Yi Sun's lab investigating the DNA sequences in genome that potentially bind to AICD binding partners has shown that various promoters of a broad set of genes can bind to Fe65 and their expressions might be influenced by Fe65/AICD.

General Notes

Table of Contents


Related URI