Document Detail


Mouse models of SCN5A-related cardiac arrhythmias.
MedLine Citation:
PMID:  19041666     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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.
Authors:
Flavien Charpentier; Anne Bourgé; Jean Mérot
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't; Review     Date:  2008-11-12
Journal Detail:
Title:  Progress in biophysics and molecular biology     Volume:  98     ISSN:  0079-6107     ISO Abbreviation:  Prog. Biophys. Mol. Biol.     Publication Date:    2008 Oct-Nov
Date Detail:
Created Date:  2009-03-16     Completed Date:  2009-05-11     Revised Date:  2011-07-22    
Medline Journal Info:
Nlm Unique ID:  0401233     Medline TA:  Prog Biophys Mol Biol     Country:  England    
Other Details:
Languages:  eng     Pagination:  230-7     Citation Subset:  IM    
Affiliation:
INSERM, UMR915, l'Institut du Thorax, F-44000 Nantes, France. flavien.charpentier@nantes.inserm.fr
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MeSH Terms
Descriptor/Qualifier:
Animals
Arrhythmias, Cardiac / etiology*,  genetics,  physiopathology
Brugada Syndrome / etiology,  genetics,  physiopathology
Disease Models, Animal
Humans
Long QT Syndrome / classification,  etiology,  genetics,  physiopathology
Mice
Mice, Knockout
Mice, Mutant Strains
Mice, Transgenic
Muscle Proteins / genetics,  physiology
Mutation
Sodium Channels / deficiency,  genetics,  physiology*
Chemical
Reg. No./Substance:
0/Muscle Proteins; 0/Scn1b protein, mouse; 0/Sodium Channels; 0/sodium channel protein type 5 subunit alpha

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