PLoS Genetics (Apr 2006)

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

DOI
https://doi.org/10.1371/journal.pgen.0020061
Journal volume & issue
Vol. 2, no. 4
p. e61

Abstract

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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.