Gene-edited zebrafish models take disease research to the next level

The zebrafish offers several distinct advantages as a genetic and embryonic model system to study human diseases for several reasons. First, the zebrafish genome contains about 80% of the human disease genes which are well conserved in their function. Second, zebrafish embryos are particular well suited for studying gene function during cardiovascular development, because zebrafish embryos are not completely dependent on a functional cardiovascular system for their development. Third, zebrafish embryos are optical transparent which makes them particularly useful for microscopic observations.

Thus far, the lack of efficient genetic tools to introduce human mutations in the zebrafish genome has hampered the study of disease mechanisms. In this paper the two groups describe an optimization of the gene-editing technique CRISPR/Cas9 in zebrafish which offers a new level of accuracy and specificity previously out of reach for research into human genetic disorders.The researchers have used CRISPR/Cas9 and a short single-stranded DNA templateto generatefour different knock-in zebrafish models for Cantú Syndrome and PLN-R14del cardiomyopathy, respectively a rare genetic disorder affecting the cardiovascular system and the most frequently carried mutation by Dutch cardiomyopathy patients. The exact replication in zebrafish of the situation in human patients is paramount for proper understanding of disease and for successful development of therapeutic strategies. Read also the Eurekalert.

Jeroen Bakkers is group leader at the Hubrecht Institute (KNAW) and Professor of Molecular Cardiogenetics at the University Medical Center Utrecht.