Department of Developmental Genetics, Max Planck Institute for Heart and Lung Research, Bad Nauheim, Germany.
DZHK German Centre for Cardiovascular Research, Partner Site Rhine-Main, Bad Nauheim, Germany.
Cardiovasc Res. 2022 Sep 20;118(12):2665-2687. doi: 10.1093/cvr/cvab310.
Mammalian models have been instrumental in investigating adult heart function and human disease. However, electrophysiological differences with human hearts and high costs motivate the need for non-mammalian models. The zebrafish is a well-established genetic model to study cardiovascular development and function; however, analysis of cardiovascular phenotypes in adult specimens is particularly challenging as they are opaque.
Here, we optimized and combined multiple imaging techniques including echocardiography, magnetic resonance imaging, and micro-computed tomography to identify and analyse cardiovascular phenotypes in adult zebrafish. Using alk5a/tgfbr1a mutants as a case study, we observed morphological and functional cardiovascular defects that were undetected with conventional approaches. Correlation analysis of multiple parameters revealed an association between haemodynamic defects and structural alterations of the heart, as observed clinically.
We report a new, comprehensive, and sensitive platform to identify otherwise indiscernible cardiovascular phenotypes in adult zebrafish.
哺乳动物模型在研究成人心功能和人类疾病方面发挥了重要作用。然而，与人类心脏的电生理差异以及高昂的成本促使人们需要寻找非哺乳动物模型。斑马鱼是一种成熟的遗传模型，可用于研究心血管发育和功能；然而，由于成年斑马鱼不透明，分析其心血管表型特别具有挑战性。
在这里，我们优化并结合了多种成像技术，包括超声心动图、磁共振成像和微计算机断层扫描，以鉴定和分析成年斑马鱼的心血管表型。我们使用 alk5a/tgfbr1a 突变体作为案例研究，观察到了常规方法无法检测到的形态和功能心血管缺陷。对多个参数的相关分析显示，血流动力学缺陷与心脏结构改变之间存在关联，这在临床上也有观察到。
我们报告了一种新的、全面的、敏感的平台，可以鉴定成年斑马鱼中原本难以察觉的心血管表型。
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