Switch to
| Predicate | Object |
|---|---|
| rdf:type | |
| lifeskim:mentions | |
| pubmed:issue |
2
|
| pubmed:dateCreated |
1996-10-24
|
| pubmed:abstractText |
Point mutations within the beta-amyloid precusor protein (beta-APP) gene known to segregate with Alzheimer's disease in certain families were introduced into human beta-APP cDNAs and expressed under the control of a neuron-specific enolase (NSE) promoter in mice. The transgenic animals exhibited transgene expression predominantly in neocortex and hippocampus where the levels were maximally 1.3-fold of those of wild-type mouse beta-APP. Quantitative immunoblot analysis in homozygous mice carrying different missense mutations showed slightly increased alpha-secretory processing. In V7171 mice compared to nontransgenic mice there was more alpha-secretory beta-APP (beta-APPsec) in cortex/hippocampus, less in cerebellum, and no difference in midbrain/brain stem. In none of the transgenic animals tested was a 4 kDa amyloid fragment detected by Western blotting of brain extracts, immunohistochemistry, or by 125I-A beta-binding onto brain sections. No glial reaction was observed. Behavioral analysis of mice carrying the V7171 mutation showed no appreciable deficit in comparison to wild-type mice. Together, these data suggest that low levels of expression of mutated beta-APP in 10-12-month-old transgenic mouse brains result in slightly more beta-APPsec, and are insufficient to induce amyloidogenic processing and AD-like pathology.
|
| pubmed:language |
eng
|
| pubmed:journal | |
| pubmed:citationSubset |
IM
|
| pubmed:chemical | |
| pubmed:status |
MEDLINE
|
| pubmed:issn |
0197-4580
|
| pubmed:author | |
| pubmed:issnType |
Print
|
| pubmed:volume |
17
|
| pubmed:owner |
NLM
|
| pubmed:authorsComplete |
Y
|
| pubmed:pagination |
205-14
|
| pubmed:dateRevised |
2010-11-18
|
| pubmed:meshHeading |
pubmed-meshheading:8744401-Alzheimer Disease,
pubmed-meshheading:8744401-Amyloid beta-Peptides,
pubmed-meshheading:8744401-Amyloidosis,
pubmed-meshheading:8744401-Animals,
pubmed-meshheading:8744401-Base Sequence,
pubmed-meshheading:8744401-Behavior, Animal,
pubmed-meshheading:8744401-Blotting, Southern,
pubmed-meshheading:8744401-Blotting, Western,
pubmed-meshheading:8744401-Humans,
pubmed-meshheading:8744401-Immunohistochemistry,
pubmed-meshheading:8744401-In Situ Hybridization,
pubmed-meshheading:8744401-Mice,
pubmed-meshheading:8744401-Mice, Inbred C57BL,
pubmed-meshheading:8744401-Mice, Transgenic,
pubmed-meshheading:8744401-Molecular Sequence Data,
pubmed-meshheading:8744401-Phosphopyruvate Hydratase,
pubmed-meshheading:8744401-Point Mutation,
pubmed-meshheading:8744401-Polymerase Chain Reaction,
pubmed-meshheading:8744401-RNA, Messenger,
pubmed-meshheading:8744401-Transgenes
|
| pubmed:articleTitle |
Lack of beta-amyloidosis in transgenic mice expressing low levels of familial Alzheimer's disease missense mutations.
|
| pubmed:affiliation |
Pharma Division, F. Hoffmann-La Roche Ltd., Basel, Switzerland.
|
| pubmed:publicationType |
Journal Article
|