title: Phenotyping structural abnormalities in mouse embryos using high-resolution episcopic microscopy.
abstract: The arrival of simple and reliable methods for 3D imaging of mouse embryos has opened the possibility of analysing normal and abnormal development in a far more systematic and comprehensive manner than has hitherto been possible. This will not only help to extend our understanding of normal tissue and organ development but, by applying the same approach to embryos from genetically modified mouse lines, such imaging studies could also transform our knowledge of gene function in embryogenesis and the aetiology of developmental disorders. The International Mouse Phenotyping Consortium is coordinating efforts to phenotype single gene knockouts covering the entire mouse genome, including characterising developmental defects for those knockout lines that prove to be embryonic lethal. Here, we present a pilot study of 34 such lines, utilising high-resolution episcopic microscopy (HREM) for comprehensive 2D and 3D imaging of homozygous null embryos and their wild-type littermates. We present a simple phenotyping protocol that has been developed to take advantage of the high-resolution images obtained by HREM and that can be used to score tissue and organ abnormalities in a reliable manner. Using this approach with embryos at embryonic day 14.5, we show the wide range of structural abnormalities that are likely to be detected in such studies and the variability in phenotypes between sibling homozygous null embryos.
authors.affiliation: Centre for Anatomy and Cell Biology & MIC, Medical University of Vienna, 1090 Wien, Austria. Wolfgang.Weninger@meduniwien.ac.at.
authors.forename: Wolfgang J
authors.initials: WJ
authors.lastname: Weninger
authors.affiliation: Centre for Anatomy and Cell Biology & MIC, Medical University of Vienna, 1090 Wien, Austria.
authors.forename: Stefan H
authors.initials: SH
authors.lastname: Geyer
authors.affiliation: MRC National Institute for Medical Research, London NW7 1AA, UK.
authors.forename: Alexandrine
authors.initials: A
authors.lastname: Martineau
authors.affiliation: Wellcome Trust Sanger Institute, Cambridge CB10 1SA, UK.
authors.forename: Antonella
authors.initials: A
authors.lastname: Galli
authors.affiliation: Wellcome Trust Sanger Institute, Cambridge CB10 1SA, UK.
authors.forename: David J
authors.initials: DJ
authors.lastname: Adams
authors.affiliation: MRC National Institute for Medical Research, London NW7 1AA, UK.
authors.forename: Robert
authors.initials: R
authors.lastname: Wilson
authors.affiliation: MRC National Institute for Medical Research, London NW7 1AA, UK.
authors.forename: Timothy J
authors.initials: TJ
authors.lastname: Mohun
mesh_terms: D000818:Animals; D004622:Embryo, Mammalian; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008853:Microscopy / Q000379:methods*; D010641:Phenotype
keywords: 3D; Episcopic; HREM; Imaging; Phenotype screen