Zebrafish Long QT Syndrome Models

Long QT syndrome (LQTS) is a cardiac disorder associated with cardiac ion channel dysfunction, characterized by prolonged QT interval, syncope, and even sudden death. To date, no suitable genetic LQTS animal model exists.

The zebrafish is a powerful vertebrate model with a heart that closely resembles that of mammals in many ways. Zebrafish heart development, starting from a single duct, develops nodular activity, atrial and ventricular separation, and coordinated interventricular conduction at 24 hours post-fertilization (hpf) and beyond 72 hours. This rapid developmental schedule allows observation of a functional heart early in development and facilitates studies such as toxicological screening, modifying mutations and developmental pathways. In addition, the small size of zebrafish larvae allows for oxygen exchange by passive diffusion, thereby improving the requirement for a functional heart pump, which allows the study of potentially severe heart defects that could lead to death in other model systems.

Fig.1 Action potentials (AP) recorded from transplanted embryonic zebrafish hearts.

Our Zebrafish Long QT Syndrome Models

Creative Biogene screened many cardiovascular mutant zebrafish for analysis by forward and reverse genetic methods, these mutants can be used for key pathways in cardiovascular development similar to higher vertebrates, and also help to develop hERG-deficient zebrafish Therapies that block off-target effects. We typically display cardiac function directly using simple motion capture or genetically encoded indicators to monitor outcome measures such as bradycardia, tachycardia, or 2:1 atrioventricular block. In addition, we provide zebrafish strains carrying precise channel variants associated with LQTS2, a model that recapitulates the human LQTS phenotype, manifested by AP prolongation and QT interval prolongation.

In conclusion, our precise gene editing technology can provide you with multiple transgenic zebrafish models of long QT syndrome that can be used to screen for human action potential duration (APD) prolongation, TdP and acquired LQTS risk Compounds, can also be used to study the role of hERG activator compounds in the more complex dynamic adaptation of APD to understand their antiarrhythmic potential.

Advantages

• Non-invasive visualization of in vivo organs and biological processes at high resolution
• Easily monitor compound effects on heart rhythm
• Examine multiple functions of genes in different mutants
• High-throughput genetic and drug screening

Creative Biogene aims to provide a suitable zebrafish model for studying human long QT syndrome, helping you to dissect the molecular pathways of cardiovascular development and disease. If you would like to learn more about zebrafish models, please feel free to contact us.

References

1. Leong IU, et al. Zebrafish as a model for long QT syndrome: the evidence and the means of manipulating zebrafish gene expression. Acta Physiol (Oxf). 2010, 199(3):257-276.
2. Arnaout R, et al. Zebrafish model for human long QT syndrome. Proc Natl Acad Sci U S A. 2007, 104(27):11316-11321.
3. Simpson KE, et al. Utility of Zebrafish Models of Acquired and Inherited Long QT Syndrome. Front Physiol. 2021, 11:624129.

For research use only. Not intended for any clinical use.