Systematic Disruption of Zebrafish Fibrillin Genes Identifies a Translational Zebrafish Model for Marfan Syndrome

斑马鱼纤连蛋白基因的系统性破坏鉴定出一种可用于研究马凡氏综合征的斑马鱼转化模型

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Abstract

Fibrillin defects lead to severe cardiovascular complications in Marfan syndrome (MFS), including aortic dilation, dissection, and rupture. To model MFS, zebrafish mutants lacking various fibrillin genes were generated. Among these mutant lines, only fibrillin-3-deficient zebrafish exhibited cardiovascular phenotypes mimicking human disease. Multimodal imaging revealed early cardiac defects, bulbus arteriosus dilation, and valve abnormalities. Transcriptomic analysis identified altered regulation of pathways related to extracellular matrix homeostasis and immune system activation. This zebrafish model, recapitulating key cardiovascular features of MFS, provides a valuable platform to investigate disease mechanisms and identify novel treatment strategies.

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