Cell and Developmental Biology Group, School of Biosciences, University of Kent, Canterbury, Kent, United Kingdom.
PLoS One. 2010 Dec 17;5(12):e14348. doi: 10.1371/journal.pone.0014348.
Dilated cardiomyopathy (DCM) is a severe cardiac condition that causes high mortality. Many genes have been confirmed to be involved in this disease. An ideal system with which to uncover disease mechanisms would be one that can measure the changes in a wide range of cardiac activities associated with mutations in specific, diversely functional cardiac genes. Such a system needs a genetically manipulable model organism that allows in vivo measurement of cardiac phenotypes and a detecting instrument capable of recording multiple phenotype parameters.
With a simple heart, a transparent body surface at larval stages and available genetic tools we chose Drosophila melanogaster as our model organism and developed for it a dual en-face/Doppler optical coherence tomography (OCT) instrument capable of recording multiple aspects of heart activity, including heart contraction cycle dynamics, ostia dynamics, heartbeat rate and rhythm, speed of heart wall movement and light reflectivity of cardiomyocytes in situ. We applied this OCT instrument to a model of Tropomyosin-associated DCM established in adult Drosophila. We show that DCM pre-exists in the larval stage and is accompanied by an arrhythmia previously unidentified in this model. We also detect reduced mobility and light reflectivity of cardiomyocytes in mutants.
These results demonstrate the capability of our OCT instrument to characterize in detail cardiac activity in genetic models for heart disease in Drosophila.
扩张型心肌病(DCM)是一种严重的心脏疾病,死亡率较高。许多基因已被证实与该病有关。一个理想的系统,可以揭示疾病机制,将是一个能够测量与特定的、多样化功能的心脏基因中的突变相关的广泛的心脏活动变化的系统。这样的系统需要一个可遗传操作的模式生物,允许活体测量心脏表型和一个能够记录多个表型参数的检测仪器。
由于心脏结构简单,幼虫阶段的体表透明,以及可用的遗传工具,我们选择黑腹果蝇作为我们的模式生物,并为其开发了一种双正面/多普勒光学相干断层扫描(OCT)仪器,能够记录心脏活动的多个方面,包括心脏收缩周期动力学、口动力学、心跳率和节律、心脏壁运动速度和心肌细胞的光反射率原位。我们将这种 OCT 仪器应用于成年果蝇中建立的肌球蛋白相关 DCM 模型。我们表明,DCM 在幼虫期就已经存在,并伴有该模型以前未识别的心律失常。我们还检测到突变体中心肌细胞的移动性和光反射率降低。
这些结果表明,我们的 OCT 仪器有能力详细描述果蝇心脏疾病遗传模型中的心脏活动。