Linked Life Data

19041666

Source:http://linkedlifedata.com/resource/pubmed/id/19041666

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
2-3
pubmed:dateCreated
2009-3-16
pubmed:abstractText
Both gain- and loss-of-function mutations in the SCN5A gene, which encodes the alpha-subunit of the cardiac voltage-gated Na+ channel Na(v)1.5, are well established to underlie hereditary arrhythmic syndromes (cardiac channelopathies) such as the type 3 long QT syndrome, cardiac conduction diseases, Brugada syndrome, sick sinus syndrome, atrial standstill and numerous overlap syndromes. Although patch-clamp studies in heterologous expression systems have provided important information to understand the genotype-phenotype relationships of these diseases, they could not clarify how mutations can be responsible for such a large spectrum of diseases, the late age of onset or the progressiveness of some of them, and for the overlapping syndromes. Genetically modified mice rapidly appeared as promising tools for understanding the pathophysiological sequence of cardiac SCN5A-related channelopathies and several mouse models have been established. Here, we review the results obtained on these models that, for most of them, convincingly recapitulate the clinical phenotypes of the patients but that also have their own limitations. Mouse models turn out to be powerful tools to elucidate the pathophysiological mechanisms of SCN5A-related diseases and offer the opportunity to investigate the cellular consequences of SCN5A mutations such as the remodelling of other gene expression that might participate in the overall phenotype and explain some of the differences among patients. Finally, they also constitute useful tools for future studies addressing as yet unanswered questions, such as the role of genetic and environmental modifiers on cardiac conduction and repolarisation.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:issn
0079-6107
pubmed:author
pubmed:issnType
Print
pubmed:volume
98
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
230-7
pubmed:dateRevised
2011-7-22
pubmed:meshHeading
pubmed:articleTitle
Mouse models of SCN5A-related cardiac arrhythmias.
pubmed:affiliation
INSERM, UMR915, l'Institut du Thorax, F-44000 Nantes, France. flavien.charpentier@nantes.inserm.fr
pubmed:publicationType
Journal Article, Review, Research Support, Non-U.S. Gov't