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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
6
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pubmed:dateCreated |
1998-12-29
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pubmed:abstractText |
Inclusion body myositis (IBM) is the most common muscle disease in the elderly. Amyloid-beta protein (A beta) has been shown to accumulate abnormally in the vacuolated fibers and to localize to amyloid-like fibrils in muscles from IBM patients. We studied the skeletal muscles from a line of transgenic mice over-expressing the carboxyl-terminal 99 amino acids (C99) of the beta-amyloid precursor protein (betaPP) with a substitution of lysine-612 to valine (K612V), intended to abolish alpha-secretase recognition and to preserve the A beta domain of C99. The majority (87%) of the 24-month-old transgenic mice showed myopathic changes, and approximately one-third of them had degenerating fibers with sarcoplasmic vacuoles and thioflavin-S-positive deposits. Ultrastructurally, the inclusions were aggregates of short thin amyloid-like fibrils, 6 to 8 nm in diameter. These features are similar to those of human IBM. Immunocytochemistry using an antibody against A beta showed membranous staining in most muscle fibers of transgenic mice, as well as granular or vacuolar cytoplasmic staining in the atrophic fibers. Western blots showed a high level of accumulation of carboxyl-terminal fragments of betaPP in the muscles of the transgenic mice with the most severe IBM-like lesions. The expression of IBM-like lesions was age dependent. These transgenic mice provide a model for the study of IBM and for the peripheral expression of a key element in the pathogenesis of Alzheimer disease.
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pubmed:grant |
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pubmed:commentsCorrections |
http://linkedlifedata.com/resource/pubmed/commentcorrection/9846957-1301020,
http://linkedlifedata.com/resource/pubmed/commentcorrection/9846957-1321564,
http://linkedlifedata.com/resource/pubmed/commentcorrection/9846957-1334198,
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http://linkedlifedata.com/resource/pubmed/commentcorrection/9846957-9846956
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
AIM
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pubmed:chemical |
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pubmed:status |
MEDLINE
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pubmed:month |
Dec
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pubmed:issn |
0002-9440
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pubmed:author |
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pubmed:issnType |
Print
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pubmed:volume |
153
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
1679-86
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pubmed:dateRevised |
2010-11-18
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pubmed:meshHeading |
pubmed-meshheading:9846957-Age Factors,
pubmed-meshheading:9846957-Animals,
pubmed-meshheading:9846957-Mice,
pubmed-meshheading:9846957-Brain,
pubmed-meshheading:9846957-Microscopy, Electron,
pubmed-meshheading:9846957-Endopeptidases,
pubmed-meshheading:9846957-Muscle, Skeletal,
pubmed-meshheading:9846957-Aspartic Acid Endopeptidases,
pubmed-meshheading:9846957-Immunohistochemistry,
pubmed-meshheading:9846957-Mutagenesis,
pubmed-meshheading:9846957-Musculoskeletal Diseases,
pubmed-meshheading:9846957-Amyloid beta-Protein Precursor,
pubmed-meshheading:9846957-Blotting, Western,
pubmed-meshheading:9846957-Amyloid beta-Peptides,
pubmed-meshheading:9846957-Mice, Transgenic,
pubmed-meshheading:9846957-Amyloid Precursor Protein Secretases
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