Systematic disruption of zebrafish fibrillin genes identifies a translational zebrafish model for Marfan syndrome

Fibrillin dysfunction in Marfan syndrome (MFS) causes severe cardiovascular complications, including aortic dilation, dissection, and rupture. To model MFS, we generated zebrafish mutants lacking various fibrillin genes. Among them, fibrillin-2b-deficient zebrafish exhibited cardiovascular phenotypes resembling those seen in patients with MFS. Multimodal imaging revealed early cardiac defects, bulbus arteriosus dilation, and valve abnormalities. RNA sequencing identified developmental disruptions, and compound testing demonstrated the model’s potential for drug discovery. This zebrafish model, recapitulating key cardiovascular features of MFS, provides a valuable platform for investigating disease mechanisms and identifying novel treatment strategies. Bulk RNA-sequencing on whole fbn2b-/- and WT control embryo's at 1 and 2 dpf, to identify early transcriptional changes during the development of the first cardiovascular phenotypes.