THE ZEBRAFISH AS A FASCINATING MODEL OF CARDIOVASCULAR DISEASES

Cardiomyopathies are a common cause of heart failure and can be inherited both monogenically and polygenically. In many patients, no causative cause can be found even after careful testing of all known disease genes. In the search for new causes of heart muscle diseases, we use a combined strategy (Figure 1). Human genetic studies and experimental approaches in the zebrafish model complement each other.

Transgenic Zebrafish

The detailed characterization of molecular signaling pathways can not only support diagnostics but also the development of targeted therapies. In order to investigate the function of disease-relevant factors in the heart, genetic model systems such as transgenic zebrafish are required. We use reverse genetics methods such as the transposon-based Tol2 system, the inducible tetracycline system, and the zinc finger nuclease-based system. The use of tissue-specific promoters allows us to comprehensively characterize the temporal expression and function of new candidate genes in vivo.

Pharmacological approaches in zebrafish

The zebrafish offers many advantages as a model organism for new treatment concepts for patients with heart disease. These include the transparency of the fish, the large number of offspring and the simple nature of pharmacological treatment. In the search for new treatment options, we are testing potentially therapeutically effective small compounds that intervene in cardiac signaling cascades in particular.

METHODOLOGIES USED WITH ZEBRAFISH

Genome editing technologies such as CRISPR together with confocal microscopy, electron microscopy, genomics and transcriptomics are heavily used in functional studies.