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Integration of multiple imaging platforms to uncover cardiac defects in adult zebrafish
bioRxiv - Developmental Biology Pub Date : 2020-05-22 , DOI: 10.1101/2020.05.21.108548
Anabela Bensimon-Brito , Giulia L. M. Boezio , João Cardeira-da-Silva , Astrid Wietelmann , Christian S. M. Helker , Radhan Ramadass , Janett Piesker , Arno Nauerth , Clemens Mueller , Didier Y. R. Stainier

Mammalian models have been instrumental to investigate adult heart function and human disease. However, electrophysiological differences with human hearts and high costs emphasize the need for additional models. The zebrafish is a well-established genetic model to study cardiac development and function; however, analysis of cardiac 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 analyze cardiac phenotypes in adult zebrafish. Using alk5a/tgfbr1a mutants as a case study, we observed morphological and functional cardiac defects, which were undetected with conventional approaches. Correlation analysis of multiple parameters revealed an association between hemodynamic defects and structural alterations of the heart, as observed clinically. Thus, we report a comprehensive and sensitive platform to identify otherwise indiscernible cardiac phenotypes in adult zebrafish, a model with clear advantages to study cardiac function and disease.

中文翻译:

集成多个成像平台以发现成年斑马鱼的心脏缺陷

哺乳动物模型有助于研究成人心脏功能和人类疾病。然而,与人心脏的电生理差异和高昂的成本强调了对其他模型的需求。斑马鱼是研究心脏发育和功能的公认遗传模型。但是,由于成人样本的心脏表型不透明,因此对其进行分析尤其具有挑战性。在这里,我们优化和组合了多种成像技术,包括超声心动图,磁共振成像和微计算机断层扫描,以识别和分析成年斑马鱼的心脏表型。使用alk5a / tgfbr1a突变体作为案例研究,我们观察到了形态学和功能性心脏缺陷,而传统方法无法检测到这些缺陷。临床上观察到,多个参数的相关性分析揭示了血液动力学缺陷与心脏结构改变之间的关联。因此,我们报告了一个全面而敏感的平台,用于识别成年斑马鱼中其他难以区分的心脏表型,该模型具有研究心脏功能和疾病的明显优势。
更新日期:2020-05-22
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