Abstract
Missense mutations in the myotilin gene cause limb-girdle muscular dystrophy type 1A (LGMD1A). We set out to examine the effect of overexpression of wild-type myotilin in an LGMD1A mouse model by crossing wild-type and mutant transgenic mice. Compared to single-transgenic mutant mice, double-transgenic mice overexpressing myotilin showed more severe muscle degeneration, enhanced myofibrillar aggregation, and earlier onset of aggregation. These data suggest that strategies aimed at lowering total myotilin levels in LGMD1A patients may be an effective therapeutic approach.
Publication types
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Comparative Study
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Research Support, N.I.H., Extramural
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Disease Models, Animal
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Humans
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Isoleucine / genetics
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Mice
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Mice, Inbred C57BL
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Mice, Transgenic
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Microfilament Proteins
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Microscopy, Electron, Transmission / methods
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Muscle Proteins / genetics
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Muscle Proteins / metabolism*
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Muscle, Skeletal / metabolism
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Muscle, Skeletal / pathology*
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Muscle, Skeletal / ultrastructure
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Muscular Dystrophies, Limb-Girdle / genetics
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Muscular Dystrophies, Limb-Girdle / metabolism*
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Muscular Dystrophies, Limb-Girdle / pathology*
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Mutation / physiology
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Threonine / genetics
Substances
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Microfilament Proteins
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Muscle Proteins
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Myot protein, mouse
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Isoleucine
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Threonine