FAD mutant PS-1 gene-targeted mice:: Increased Aβ42 and Aβ deposition without APP overproduction
FAD mutant PS-1 gene-targeted mice:: Increased Aβ42 and Aβ deposition without APP overproduction
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DOI：
10.1016/s0197-4580(01)00330-x
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发表时间：
2002-05-01
影响因子：
4.2
通讯作者：
Scott, RW
中科院分区：
文献类型：
--
作者：
Flood, DG;Reaume, AG;Scott, RW
To investigate the consequences of mutant presenilin-1 (PS-1) expression under the control of the normal PS-1 gene, a gene-targeted mouse bearing the FAD mutation P264L was made. Gene-targeted models are distinct from transgenic models because the mutant gene is expressed at normal levels, in the absence of the wild-type protein. PS-1(P264L/P264L) mice had normal expression of PS-1 mRNA, but levels of the N- and C-terminal protein fragments of PS-1, ere reduced while levels of the holoprotein were increased. When crossed into Tg(HuAPP695.K670N/M671L)2576 mice, the PS-1(P264L) mutation accelerated the onset of amyloid (Abeta) deposition in a gene-dosage dependent manner, Tg2576/PS-1(P264L/P264L) mice also had Abeta deposition that was widely distributed throughout the brain and spinal cord. App(NLh/NLh)/PS-1(P264L/P264L) double gene-targeted mice had elevated levels of Abeta42, sufficient to cause Abeta deposition beginning at 6 months of age. Abeta deposition increased linearly over time in APP(NLh/NLh)/PS-1P(264L/P264L) mice, whereas the increase in Tg-2576 mice was exponential. The APP(NLh/NLh)/PS-1(P264L/P264L) double gene-targeted mouse represents an animal model that exhibits Abeta deposition without overexpression of APP. (C) 2002 Elsevier Science Inc. All rights reserved.
