Title: FAD mutant PS-1 gene-targeted mice: increased A beta 42 and A beta deposition without APP overproduction
Authors: Flood, Dorothy G ×
Reaume, Andrew G
Dorfman, Karen S
Lin, Yin Guo
Lang, Diane M
Trusko, Stephen P
Savage, Mary J
Annaert, Wim
De Strooper, Bart
Siman, Robert
Scott, Richard W #
Issue Date: Apr-2002
Publisher: Elsevier
Series Title: Neurobiology of Aging vol:23 issue:3 pages:335-48
Abstract: 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 were 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-1(P264L/P264L) mice, whereas the increase in Tg2576 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.
ISSN: 0197-4580
Publication status: published
KU Leuven publication type: IT
Appears in Collections:Molecular Genetics Section (-)
Department of Human Genetics - miscellaneous
× corresponding author
# (joint) last author

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