Linked Life Data

15525659

Source:http://linkedlifedata.com/resource/pubmed/id/15525659

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
1
pubmed:dateCreated
2004-12-17
pubmed:abstractText
Mutations in the MYBPC3 gene encoding human cardiac myosin-binding protein-C (cMyBP-C) are associated with familial hypertrophic cardiomyopathy (FHC), but the molecular mechanisms involved are not fully understood. In addition, development of FHC is sensitive to genetic background, and the search for candidate modifier genes is crucial with a view to proposing diagnosis and exploring new therapies. We used Drosophila as the model to investigate the in vivo consequences of human cMyBP-C mutations. We first produced transgenic flies that specifically express human wild-type or two C-terminal truncated cMyBP-Cs in indirect flight muscles (IFM), a tissue particularly amenable to genetic and molecular analyses. First, incorporation of human cMyBP-C into the IFM led to sarcomeric structural abnormalities and to a flightless phenotype aggravated by age and human gene dosage. Second, transcriptome analysis of transgenic IFM using nylon microarrays showed the remodelling of a transcriptional program involving 97 out of 3570 Drosophila genes. Among them, the Calmodulin gene encoding a key component of muscle contraction, found up-regulated in transgenic IFM, was evaluated as a potential modifier gene. Calmodulin mutant alleles rescued the flightless phenotype, and therefore behave as dominant suppressors of the flightless phenotype suggesting that Calmodulin might be a modifier gene in the context of human FHC. In conclusion, we suggest that the combination of heterologous transgenesis and transcriptome analysis in Drosophila could be of great value as a way to glean insights into the molecular mechanisms underlying FHC and to propose potential candidate modifier genes.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jan
pubmed:issn
0964-6906
pubmed:author
pubmed:issnType
Print
pubmed:day
1
pubmed:volume
14
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
7-17
pubmed:dateRevised
2006-11-15
pubmed:meshHeading
pubmed:year
2005
pubmed:articleTitle
Expression of cardiac myosin-binding protein-C (cMyBP-C) in Drosophila as a model for the study of human cardiomyopathies.
pubmed:affiliation
CNRS, UMR6545, LGPD-IBDM, Université de la Méditerranée, Marseille, France.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't