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 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.
Johnson
John T
JT
Scientific Computing and Imaging Institute, University of Utah, Salt Lake City, Utah, United States of America.
Hansen
Mark S
MS
Wu
Isabel
I
Healy
Lindsey J
LJ
Johnson
Christopher R
CR
Jones
Greg M
GM
Capecchi
Mario R
MR
Keller
Charles
C