Virtual histology of transgenic mouse embryos for high-throughput phenotyping

John T. Johnson, Mark S. Hansen, Isabel Wu, Lindsey J. Healy, Christopher R. Johnson, Greg M. Jones, Mario R. Capecchi, Charles Keller

    Research output: Contribution to journalArticlepeer-review

    136 Scopus citations

    Abstract

    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 μm or 8 μm 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.

    Original languageEnglish (US)
    Article numbere61
    Pages (from-to)471-477
    Number of pages7
    JournalPLoS genetics
    Volume2
    Issue number4
    DOIs
    StatePublished - Apr 2006

    ASJC Scopus subject areas

    • Ecology, Evolution, Behavior and Systematics
    • Molecular Biology
    • Genetics
    • Genetics(clinical)
    • Cancer Research

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