Geyer Stefan H, Reissig Lukas F, Hüsemann Markus, Höfle Cordula, Wilson Robert, Prin Fabrice, Szumska Dorota, Galli Antonella, Adams David J, White Jacqui, Mohun Timothy J, Weninger Wolfgang J
Division of Anatomy & MIC, Medical University of Vienna, Vienna, Austria.
The Francis Crick Institute, London, UK.
J Anat. 2017 Oct;231(4):600-614. doi: 10.1111/joa.12663. Epub 2017 Aug 3.
Accurate identification of abnormalities in the mouse embryo depends not only on comparisons with appropriate, developmental stage-matched controls, but also on an appreciation of the range of anatomical variation that can be expected during normal development. Here we present a morphological, topological and metric analysis of the heart and arteries of mouse embryos harvested on embryonic day (E)14.5, based on digital volume data of whole embryos analysed by high-resolution episcopic microscopy (HREM). By comparing data from 206 genetically normal embryos, we have analysed the range and frequency of normal anatomical variations in the heart and major arteries across Theiler stages S21-S23. Using this, we have identified abnormalities in these structures among 298 embryos from mutant mouse lines carrying embryonic lethal gene mutations produced for the Deciphering the Mechanisms of Developmental Disorders (DMDD) programme. We present examples of both commonly occurring abnormal phenotypes and novel pathologies that most likely alter haemodynamics in these genetically altered mouse embryos. Our findings offer a reference baseline for identifying accurately abnormalities of the heart and arteries in embryos that have largely completed organogenesis.
准确识别小鼠胚胎中的异常不仅取决于与发育阶段匹配的适当对照进行比较，还取决于对正常发育过程中预期的解剖变异范围的认识。在此，我们基于通过高分辨率表面显微镜（HREM）分析的全胚胎数字体积数据，对胚胎第14.5天（E14.5）收获的小鼠胚胎的心脏和动脉进行了形态学、拓扑学和度量分析。通过比较来自206个基因正常胚胎的数据，我们分析了Theiler阶段S21 - S23中心脏和主要动脉正常解剖变异的范围和频率。利用这些数据，我们在为“解读发育障碍机制（DMDD）”项目产生的携带胚胎致死基因突变的突变小鼠品系的298个胚胎中，识别出了这些结构的异常。我们展示了常见异常表型和可能改变这些基因改变的小鼠胚胎血流动力学的新病理情况的实例。我们的研究结果为准确识别已基本完成器官发生的胚胎中心脏和动脉的异常提供了参考基线。
