Department of Medical Biophysics, University of Toronto, and Hospital for Sick Children, Toronto, ON M5G 2M9, Canada.
Development. 2012 Sep;139(17):3248-56. doi: 10.1242/dev.082016.
The goal of the International Mouse Phenotyping Consortium (IMPC) is to phenotype targeted knockout mouse strains throughout the whole mouse genome (23,000 genes) by 2021. A significant percentage of the generated mice will be embryonic lethal; therefore, phenotyping methods tuned to the mouse embryo are needed. Methods that are robust, quantitative, automated and high-throughput are attractive owing to the numbers of mice involved. Three-dimensional (3D) imaging is a useful method for characterizing morphological phenotypes. However, tools to automatically quantify morphological information of mouse embryos from 3D imaging have not been fully developed. We present a representative mouse embryo average 3D atlas comprising micro-CT images of 35 individual C57BL/6J mouse embryos at 15.5 days post-coitum. The 35 micro-CT images were registered into a consensus average image with our automated image registration software and 48 anatomical structures were segmented manually. We report the mean and variation in volumes for each of the 48 segmented structures. Mouse organ volumes vary by 2.6-4.2% on a linear scale when normalized to whole body volume. A power analysis of the volume data reports that a 9-14% volume difference can be detected between two classes of mice with sample sizes of eight. This resource will be crucial in establishing baseline anatomical phenotypic measurements for the assessment of mutant mouse phenotypes, as any future mutant embryo image can be registered to the atlas and subsequent organ volumes calculated automatically.
国际小鼠表型分析联盟（IMPC）的目标是在 2021 年前对靶向敲除小鼠品系进行全基因组表型分析（23000 个基因）。由于大量的基因被敲除，产生的小鼠中有相当大比例是胚胎致死的；因此，需要针对小鼠胚胎进行表型分析方法的调整。由于涉及的小鼠数量众多，稳健、定量、自动化和高通量的方法很有吸引力。三维（3D）成像技术是一种用于描述形态表型的有用方法。然而，尚未完全开发出从 3D 成像中自动量化小鼠胚胎形态信息的工具。我们提出了一个具有代表性的小鼠胚胎平均 3D 图谱，该图谱包含了 35 只 C57BL/6J 小鼠胚胎在受精后 15.5 天的微 CT 图像。这 35 张微 CT 图像通过我们的自动图像配准软件配准到一个共识平均图像中，并手动分割了 48 个解剖结构。我们报告了 48 个分割结构中每个结构的体积均值和变异。当标准化为全身体积时，48 个分割结构的体积变化范围为 2.6%-4.2%。对体积数据的幂分析报告称，在样本量为 8 的情况下，两个类别的小鼠之间可以检测到 9-14%的体积差异。这个资源对于建立用于评估突变小鼠表型的基线解剖学表型测量至关重要，因为任何未来的突变胚胎图像都可以注册到图谱中，并自动计算随后的器官体积。
