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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
3
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pubmed:dateCreated |
2002-4-17
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pubmed:abstractText |
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.
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
IM
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pubmed:chemical |
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pubmed:status |
MEDLINE
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pubmed:issn |
0197-4580
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pubmed:author |
pubmed-author:AnnaertWim GWG,
pubmed-author:De StrooperBartB,
pubmed-author:DorfmanKaren SKS,
pubmed-author:FloodDorothy GDG,
pubmed-author:LangDiane MDM,
pubmed-author:LinYin GuoYG,
pubmed-author:ReaumeAndrew GAG,
pubmed-author:SavageMary JMJ,
pubmed-author:ScottRichard WRW,
pubmed-author:SimanRobertR,
pubmed-author:TruskoStephen PSP
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pubmed:issnType |
Print
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pubmed:volume |
23
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
335-48
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pubmed:dateRevised |
2010-11-18
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pubmed:meshHeading |
pubmed-meshheading:11959395-Alzheimer Disease,
pubmed-meshheading:11959395-Amino Acid Sequence,
pubmed-meshheading:11959395-Amino Acid Substitution,
pubmed-meshheading:11959395-Amyloid beta-Peptides,
pubmed-meshheading:11959395-Amyloid beta-Protein Precursor,
pubmed-meshheading:11959395-Animals,
pubmed-meshheading:11959395-Cell Line,
pubmed-meshheading:11959395-Female,
pubmed-meshheading:11959395-Gene Targeting,
pubmed-meshheading:11959395-Genotype,
pubmed-meshheading:11959395-Humans,
pubmed-meshheading:11959395-Membrane Proteins,
pubmed-meshheading:11959395-Mice,
pubmed-meshheading:11959395-Mice, Inbred C57BL,
pubmed-meshheading:11959395-Mice, Mutant Strains,
pubmed-meshheading:11959395-Mice, Transgenic,
pubmed-meshheading:11959395-Molecular Sequence Data,
pubmed-meshheading:11959395-Mutation,
pubmed-meshheading:11959395-Neocortex,
pubmed-meshheading:11959395-Peptide Fragments,
pubmed-meshheading:11959395-Pregnancy,
pubmed-meshheading:11959395-Presenilin-1,
pubmed-meshheading:11959395-RNA, Messenger
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pubmed:articleTitle |
FAD mutant PS-1 gene-targeted mice: increased A beta 42 and A beta deposition without APP overproduction.
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pubmed:affiliation |
Department of Neurobiology, Cephalon, Inc., West Chester, PA 19380, USA. dflood@cephalon.com
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pubmed:publicationType |
Journal Article,
Comparative Study
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