Source:http://linkedlifedata.com/resource/pubmed/id/17901043
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| Predicate | Object |
|---|---|
| rdf:type | |
| lifeskim:mentions | |
| pubmed:issue |
24
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| pubmed:dateCreated |
2007-11-20
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| pubmed:abstractText |
We investigated whether or not human disease-causing, amino acid substitutions in MYH9 could cause dominant phenotypes when introduced into the sole non-muscle myosin II heavy chain in Drosophila melanogaster (zip/MyoII). We characterized in vivo the effects of four MYH9-like mutations in the myosin rod-R1171C, D1430N, D1847K and R1939X-which occur at highly conserved residues. These engineered mutant heavy chains resulted in D. melanogaster non-muscle myosin II with partial wild-type function. In a wild-type genetic background, mutant heavy chains were overtly recessive and hypomorphic: each was able to substitute partially for endogenous non-muscle myosin II heavy chain in animals lacking zygotically produced heavy chain (but the penetrance of rescue was below Mendelian expectation). Moreover, each of the four mutant heavy chains exhibits dominant characteristics when expressed in a sensitized genetic background (flies heterozygous for RhoA mutations). Thus, these zip/MyoII(MYH9) alleles function, like certain other hypomorphic alleles, as excellent bait in screens for genetic interactors. Our conjecture is that these mutations in D. melanogaster behave comparably to their parent mutations in humans. We further characterized these zip/MyoII(MYH9) alleles, and found that all were capable of correct spatial and temporal localization in animals lacking zygotic expression of wild-type zip/MyoII. In vitro, we demonstrate that mutant heavy chains can dimerize with endogenous, wild-type heavy chains, fold into coiled-coil structures and assemble into higher-order structures. Our work further supports D. melanogaster as a model system for investigating the basis of human disease.
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| pubmed:grant | |
| pubmed:language |
eng
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| pubmed:journal | |
| pubmed:citationSubset |
IM
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| pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Drosophila Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/MYH9 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Membrane Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Molecular Motor Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Myosin Heavy Chains,
http://linkedlifedata.com/resource/pubmed/chemical/zipper protein, Drosophila
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| pubmed:status |
MEDLINE
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| pubmed:month |
Dec
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| pubmed:issn |
0964-6906
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| pubmed:author | |
| pubmed:issnType |
Print
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| pubmed:day |
15
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| pubmed:volume |
16
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| pubmed:owner |
NLM
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| pubmed:authorsComplete |
Y
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| pubmed:pagination |
3160-73
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| pubmed:meshHeading |
pubmed-meshheading:17901043-Alleles,
pubmed-meshheading:17901043-Amino Acid Sequence,
pubmed-meshheading:17901043-Animals,
pubmed-meshheading:17901043-Animals, Genetically Modified,
pubmed-meshheading:17901043-Blood Platelet Disorders,
pubmed-meshheading:17901043-Crosses, Genetic,
pubmed-meshheading:17901043-Disease Models, Animal,
pubmed-meshheading:17901043-Drosophila,
pubmed-meshheading:17901043-Drosophila Proteins,
pubmed-meshheading:17901043-Genes, Dominant,
pubmed-meshheading:17901043-Humans,
pubmed-meshheading:17901043-Membrane Proteins,
pubmed-meshheading:17901043-Models, Biological,
pubmed-meshheading:17901043-Molecular Motor Proteins,
pubmed-meshheading:17901043-Molecular Sequence Data,
pubmed-meshheading:17901043-Mutagenesis, Site-Directed,
pubmed-meshheading:17901043-Myosin Heavy Chains,
pubmed-meshheading:17901043-Phenotype,
pubmed-meshheading:17901043-Sequence Homology, Amino Acid,
pubmed-meshheading:17901043-Transgenes
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| pubmed:year |
2007
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| pubmed:articleTitle |
An MYH9 human disease model in flies: site-directed mutagenesis of the Drosophila non-muscle myosin II results in hypomorphic alleles with dominant character.
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| pubmed:affiliation |
Department of Biology, DCMB Group, Duke University, Durham, NC 27708-0338, USA.
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| pubmed:publicationType |
Journal Article,
Research Support, N.I.H., Extramural
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