Virtual Histology of Transgenic Mouse Embryos for High-Throughput Phenotyping

Virtual Histology of Transgenic Mouse Embryos for High-Throughput Phenotyping

Info iconThis preview shows pages 1–2. Sign up to view the full content.

View Full Document Right Arrow Icon
Virtual Histology of Transgenic Mouse Embryos for High-Throughput Phenotyping John T. Johnson 1 [ , Mark S. Hansen 2 [ , Isabel Wu 3 , Lindsey J. Healy 1 , Christopher R. Johnson 1 , Greg M. Jones 1 , Mario R. Capecchi 4,5 , Charles Keller 3* 1 Scientific Computing and Imaging Institute, University of Utah, Salt Lake City, Utah, United States of America, 2 Division of Pediatric Hematology-Oncology, Department of Pediatrics, University of Utah, Salt Lake City, Utah, United States of America, 3 Department of Cellular & Structural Biology and Department of Pediatrics, Children’s Cancer Research Institute, The University of Texas Health Science Center, San Antonio, Texas, United States of America, 4 Department of Human Genetics, University of Utah, Salt Lake City, Utah, United States of America, 5 Howard Hughes Medical Institute, University of Utah, Salt Lake City, Utah, United States of America 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 l mor8 l 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. Citation: Johnson JT, Hansen MS, Wu I, Healy LJ, Johnson CR, et al. (2006) Virtual histology of transgenic mouse embryos for high-throughput phenotyping. PLoS Genet 2(4): e61. DOI: 10.1371/journal.pgen.0020061 Introduction Gene targeting in mice allows unprecedented insight into the function of genes and their roles in patterning the mammalian embryo [1]. A full understanding of mammalian development by this means, using the gene-targeting ap- proach for every one of the approximately 25,000 or more mouse genes, may seem like a daunting task. Nevertheless, more than 10% of known mouse genes have already been disrupted by gene targeting. Moreover, the National Institutes of Health is leading an effort to create a collection of mouse lines with disruption of every known gene [2]. The challenge laid before developmental biologists will be to systemically analyze morphological phenotypes and, where possible, determine the quantitative contribution of each gene towards patterning of the embryo. Tools for this type of ‘‘ phenomic ’’ analysis must include rapid, inexpensive, and accessible high- throughput methods of high-resolution anatomical imaging
Background image of page 1

Info iconThis preview has intentionally blurred sections. Sign up to view the full version.

View Full DocumentRight Arrow Icon
Image of page 2
This is the end of the preview. Sign up to access the rest of the document.

This note was uploaded on 05/28/2010 for the course BIOLOGY 03234 taught by Professor Sochacka during the Spring '10 term at Ghent University.

Page1 / 7

Virtual Histology of Transgenic Mouse Embryos for High-Throughput Phenotyping

This preview shows document pages 1 - 2. Sign up to view the full document.

View Full Document Right Arrow Icon
Ask a homework question - tutors are online