APP processing and synaptic plasticity in presenilin-1 conditional knockout mice

Huakui Yu, Carlos A. Saura, Se Young Choi, Linus D. Sun, Xudong Yang, Melissa Handler, Takeshi Kawarabayashi, Linda Younkin, Bogdan Fedeles, Matthew A. Wilson, Steve Younkin, Eric R. Kandel, Alfredo Kirkwood, Jie Shen

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203 Scopus citations

Abstract

We have developed a presenilin-1 (PS1) conditional knockout mouse (cKO), in which PS1 inactivation is restricted to the postnatal forebrain. The PS1 cKO mouse is viable and exhibits no gross abnormalities. The carboxy-terminal fragments of the amyloid precursor protein differentially accumulate in the cerebral cortex of cKO mice, while generation of β-amyloid peptides is reduced. Expression of Notch downstream effector genes, Hes1, Hes5, and Dll1, is unaffected in the cKO cortex. Although basal synaptic transmission, long-term potentiation, and long-term depression at hippocampal area CA1 synapses are normal, the PS1 cKO mice exhibit subtle but significant deficits in long-term spatial memory. These results demonstrate that inactivation of PS1 function in the adult cerebral cortex leads to reduced Aβ generation and subtle cognitive deficits without affecting expression of Notch downstream genes.

Original languageEnglish (US)
Pages (from-to)713-726
Number of pages14
JournalNeuron
Volume31
Issue number5
DOIs
StatePublished - Sep 13 2001

ASJC Scopus subject areas

  • Neuroscience(all)

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    Yu, H., Saura, C. A., Choi, S. Y., Sun, L. D., Yang, X., Handler, M., Kawarabayashi, T., Younkin, L., Fedeles, B., Wilson, M. A., Younkin, S., Kandel, E. R., Kirkwood, A., & Shen, J. (2001). APP processing and synaptic plasticity in presenilin-1 conditional knockout mice. Neuron, 31(5), 713-726. https://doi.org/10.1016/S0896-6273(01)00417-2