Phenotypic annotation of the mouse X chromosome
- Brian J. Cox1,12,
- Marion Vollmer2,12,
- Owen Tamplin1,3,12,
- Mei Lu1,
- Steffen Biechele1,3,
- Marina Gertsenstein4,5,
- Claude van Campenhout2,
- Thomas Floss6,
- Ralf Kühn6,
- Wolfgang Wurst6,7,8,9,10,
- Heiko Lickert2,13 and
- Janet Rossant1,3,11,13
- 1Program in Developmental and Stem Cell Biology, The Hospital for Sick Children Research Institute, Toronto, Ontario M5G 1L7, Canada;
- 2Institute of Stem Cell Research, Helmholtz Zentrum München, German Research Center for Environmental Health (GmbH), Neuherberg 85764, Germany;
- 3Department of Molecular Genetics, University of Toronto, Toronto, Ontario M5S 1A8, Canada;
- 4Samuel Lunenfeld Research Institute, Mount Sinai Hospital, Toronto, Ontario M5G 1X5, Canada;
- 5Toronto Centre for Phenogenomics, Transgenic Core, Toronto M5T 3H7, Canada;
- 6Institute of Developmental Genetics, Helmholtz Zentrum München, German Research Center for Environmental Health (GmbH), Neuherberg 85764, Germany;
- 7MPI für Psychiatrie, München 80804, Germany;
- 8Helmholtz Zentrum München, German Research Center for Environmental Health Institute of Developmental Genetics, Neuherberg 85764, Germany;
- 9Technical University Weihenstephan, Lehrstuhl für Entwicklungsgenetik, c/o Helmholtz Zentrum München, Neuherberg 85764, Germany;
- 10Deutsches Zentrum für Neurodegenerative Erkrankungen e. V. (DZNE), Standort München, München 80336, Germany;
- 11Department of Obstetrics and Gynecology, University of Toronto, Toronto, Ontario M5T 3H7, Canada
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↵12 These authors contributed equally to this work.
Abstract
Mutational screens are an effective means used in the functional annotation of a genome. We present a method for a mutational screen of the mouse X chromosome using gene trap technologies. This method has the potential to screen all of the genes on the X chromosome without establishing mutant animals, as all gene-trapped embryonic stem (ES) cell lines are hemizygous null for mutations on the X chromosome. Based on this method, embryonic morphological phenotypes and expression patterns for 58 genes were assessed, ∼10% of all human and mouse syntenic genes on the X chromosome. Of these, 17 are novel embryonic lethal mutations and nine are mutant mouse models of genes associated with genetic disease in humans, including BCOR and PORCN. The rate of lethal mutations is similar to previous mutagenic screens of the autosomes. Interestingly, some genes associated with X-linked mental retardation (XLMR) in humans show lethal phenotypes in mice, suggesting that null mutations cannot be responsible for all cases of XLMR. The entire data set is available via the publicly accessible website (http://xlinkedgenes.ibme.utoronto.ca/).
Footnotes
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↵13 Corresponding authors.
E-mail janet.rossant{at}sickkids.ca.
E-mail heiko.lickert{at}helmholtz-muenchen.de.
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[Supplemental material is available online at http://www.genome.org. Phenotype data and images of analyzed cell lines have been submitted to Mouse Genome Informatics (http://www.informatics.jax.org) under the allele IDs listed in Supplemental Table 2.]
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Article published online before print. Article and publication date are at http://www.genome.org/cgi/doi/10.1101/gr.105106.110.
- Received January 11, 2010.
- Accepted May 11, 2010.
- Copyright © 2010 by Cold Spring Harbor Laboratory Press
