PUBLICATION
Zebrafish as a model for Long QT syndrome: the evidence, and the means of manipulating zebrafish gene expression
- Authors
- Leong, I.U., Skinner, J.R., Shelling, A.N., and Love, D.R.
- ID
- ZDB-PUB-100330-13
- Date
- 2010
- Source
- Acta physiologica (Oxford, England) 199(3): 257-276 (Review)
- Registered Authors
- Love, Donald R.
- Keywords
- Zebrafish, long QT syndrome, gene manipulation, models
- MeSH Terms
-
- Animals
- Disease Models, Animal
- Electrocardiography
- Electrophysiology
- Gene Expression/genetics*
- Heart/anatomy & histology
- Heart/physiology
- Humans
- Long QT Syndrome/genetics*
- Long QT Syndrome/physiopathology
- Mice
- Zebrafish/physiology*
- PubMed
- 20331541 Full text @ Acta Physiol. (Oxf).
Citation
Leong, I.U., Skinner, J.R., Shelling, A.N., and Love, D.R. (2010) Zebrafish as a model for Long QT syndrome: the evidence, and the means of manipulating zebrafish gene expression. Acta physiologica (Oxford, England). 199(3):257-276.
Abstract
Congenital long QT syndrome (LQT) is a group of cardiac disorders associated with the dysfunction of cardiac ion channels. It is characterised by prolongation of the QT-interval, episodes of syncope and even sudden death. Individuals may remain asymptomatic for most of their lives while others present with severe symptoms. This heterogeneity in phenotype makes diagnosis difficult with a greater emphasis on more targeted therapy. As a means of understanding the molecular mechanisms underlying LQT syndrome, evaluating the effect of modifier genes on disease severity, as well as to test new therapies, the development of model systems remains an important research tool. Mice have predominantly been the animal model of choice for cardiac arrhythmia research, but there have been varying degrees of success in recapitulating the human symptoms; the mouse cardiac action potential and surface ECG exhibit major differences from those of the human heart. Against this background, the zebrafish is an emerging vertebrate disease modelling species that offers advantages in analysing LQT syndrome, not least because its cardiac action potential much more closely resembles that of the human. This article highlights the use and potential of this species in LQT syndrome modelling, and as a platform for the in vivo assessment of putative disease-causing mutations in LQT genes, and of therapeutic interventions.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping