TY - JOUR
T1 - APP processing and synaptic plasticity in presenilin-1 conditional knockout mice
AU - Yu, Huakui
AU - Saura, Carlos A.
AU - Choi, Se Young
AU - Sun, Linus D.
AU - Yang, Xudong
AU - Handler, Melissa
AU - Kawarabayashi, Takeshi
AU - Younkin, Linda
AU - Fedeles, Bogdan
AU - Wilson, Matthew A.
AU - Younkin, Steve
AU - Kandel, Eric R.
AU - Kirkwood, Alfredo
AU - Shen, Jie
N1 - Funding Information:
The authors would like to thank Wen Cheng and Eddie Meloni for technical assistance, Dennis Selkoe and Bing Zheng for APP antibodies and ELISA measurements of human Aβ peptides, Lennart Mucke for the APP transgenic mice, Mikio Shoji for the “Saeko” antiserum, Gopal Thinakaran for PS1 and Takeshi Iwatsubo for PS2 antisera, Peter St. George-Hyslop for PS2, and Ryoichiro Kageyama for Hes1, Hes5, and Dll1 plasmids. This work was supported in part by grants from NIH and Alzheimer's Association.
PY - 2001/9/13
Y1 - 2001/9/13
N2 - 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.
AB - 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.
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U2 - 10.1016/S0896-6273(01)00417-2
DO - 10.1016/S0896-6273(01)00417-2
M3 - Article
C2 - 11567612
AN - SCOPUS:17944376442
SN - 0896-6273
VL - 31
SP - 713
EP - 726
JO - Neuron
JF - Neuron
IS - 5
ER -