High-throughput analysis of mouse embryos by magnetic resonance imaging.

Abstract

Genetic studies in the mouse are crucial for uncovering new genes and signaling pathways associated with development. The identification of murine models with developmental malformations in high-throughput mutagenesis screens is made difficult because, after mid-embryogenesis, the embryo is opaque. Traditional phenotyping methods such as histological sectioning are labor intensive and destructive. We have developed and optimized a novel method for high-throughput multiembryo magnetic resonance imaging (MRI). Here we present our method for processing 32 mouse embryos for analysis by MRI. We describe the MR system, imaging software, and the reconstruction of two-dimensional (2D) and three-dimensional (3D) images. We also discuss the applications of this technique, highlight its advantages, and point out some disadvantages. Using this approach, we can identify developmental malformations in mutant embryos at high spatial resolution (voxel size 25.4 × 25.4 × 24.4 µm). This technique can be easily used for mouse mutagenesis screens and thus provides an important tool for identifying new mouse models for human diseases.