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Dis Model Mech. 2012 Jan;5(1):19-25. doi: 10.1242/dmm.008334. Epub 2011 Oct 25.

Exploring the elephant: histopathology in high-throughput phenotyping of mutant mice.

Author information

1
Department of Physiology, Development and Neuroscience, University of Cambridge, Downing Street, Cambridge, CB2 3EG, UK. ps@mole.bio.cam.ac.uk

Abstract

Recent advances in gene knockout techniques and the in vivo analysis of mutant mice, together with the advent of large-scale projects for systematic mouse mutagenesis and genome-wide phenotyping, have allowed the creation of platforms for the most complete and systematic analysis of gene function ever undertaken in a vertebrate. The development of high-throughput phenotyping pipelines for these and other large-scale projects allows investigators to search and integrate large amounts of directly comparable phenotype data from many mutants, on a genomic scale, to help develop and test new hypotheses about the origins of disease and the normal functions of genes in the organism. Histopathology has a venerable history in the understanding of the pathobiology of human and animal disease, and presents complementary advantages and challenges to in vivo phenotyping. In this review, we present evidence for the unique contribution that histopathology can make to a large-scale phenotyping effort, using examples from past and current programmes at Lexicon Pharmaceuticals and The Jackson Laboratory, and critically assess the role of histopathology analysis in high-throughput phenotyping pipelines.

PMID:
22028326
PMCID:
PMC3255539
DOI:
10.1242/dmm.008334
[Indexed for MEDLINE]
Free PMC Article
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