Zebrafish Arrhythmia Models

Spontaneous arrhythmias have proven difficult to model in vivo, in part because of our incomplete understanding of the etiology of most clinical rhythm disturbances. A variety of factors, including genetic susceptibility, extrinsic injury, environmental exposure, and stochastic processes, contribute to the eventual arrhythmia. An ideal animal model recapitulates not only the individual components of the causal chain leading to arrhythmias, but also every step of the process. Despite the large number of animal models, several areas of in vivo electrophysiology remain relatively inaccessible, including: developmental patterns of cardiac excitability and coupling, in vivo cell biology and efficient identification of channel partner proteins.

Over the past decade, the zebrafish has emerged as a major genetic model organism that replicates human cardiac diseases, including arrhythmias, in vivo. The potential of zebrafish for in vivo cell biology, physiology, disease modeling, and drug discovery has begun to be realized. Zebrafish phenotypes can be easily identified, which has led to their use in many genetic and chemical screens. Additionally, zebrafish are able to survive for days without any cardiovascular function by diffusion alone, enabling screening for extreme phenotypes.

Fig.1 Stages of cardiac development in zebrafish from 10 to 96 hours post-fertilization (hpf).

Our Zebrafish Arrhythmia Models

Creative Biogene has established a variety of zebrafish arrhythmia models through genetic manipulation. We combine rapid genetic manipulation and high-resolution physiology to define the endocardial signaling required to pattern central slow conducting tissue, helping you uncover distinct local endocardial-myocardial interactions within the developing heart tube for arrhythmia Disease initiation and pathogenesis provide unique insights. Thus, in addition, our zebrafish model can be used for inhibitory screening to identify novel chemical modulators of disease phenotypes or novel arrhythmogenic substrates.

Table 1 Zebrafish models of cardiac arrhythmia.

Advantages

• Dynamic monitoring of various cellular processes in vivo by real-time imaging of fluorescent reporter lines
• Fluorescent markers highlight the location or activity of specific cell populations
• Ability to screen for extreme phenotypes
• High-throughput genetic and drug screening

References

1. Gauvrit S, et al. Modeling Human Cardiac Arrhythmias: Insights from Zebrafish. J Cardiovasc Dev Dis. 2022, 9(1):13.
2. Milan DJ, Macrae CA. Zebrafish genetic models for arrhythmia. Prog Biophys Mol Biol. 2008, 98(2-3):301-308.

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