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Virtual histology of transgenic mouse embryos for high-throughput phenotyping.

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Author(s): Johnson John T | Hansen Mark S | Wu Isabel | Healy Lindsey J | Johnson Christopher R | Jones Greg M | Capecchi Mario R | Keller Charles

Journal: PLoS Genetics
ISSN 1553-7390

Volume: 2;
Issue: 4;
Start page: e61;
Date: 2006;
Original page

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 mum or 8 mum 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.
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