Virtual histology of transgenic mouse embryos for high-throughput phenotyping

A bold new effort to disrupt every gene in the mouse genome necessitates systematic, interdisciplinary approaches to analyzing patterning defects in the mouse embryo. We present a novel, rapid, and inexpensive method for obtaining high-resolution virtual histology for phenotypic assessment of mouse embryos. Using osmium tetroxide to differentially stain tissues followed by volumetric X-ray computed tomography to image whole embryos, isometric resolutions of 27 mu m or 8 mu m were achieved with scan times of 2 h or 12 h, respectively, using mid- gestation E9.5 - E12.5 embryos. The datasets generated by this method are immediately amenable to state- of- the- art computational methods of organ patterning analysis. This technique to assess embryo anatomy represents a significant improvement in resolution, time, and expense for the quantitative, three- dimensional analysis of developmental patterning defects attributed to genetically engineered mutations and chemically induced embryotoxicity.