Phenotypic annotation of the mouse X chromosome
- Brian J. Cox1,6,
- Marion Vollmer2,
- Owen Tamplin3,
- Mei Lu4,
- Steffen Biechele4,
- Thomas Floss2,
- Marina Gertsenstein5,
- Claude van Campenhout2,
- Ralf Kühn2,
- Wolfgang Wurst2,
- Heiko Lickert2 and
- Janet Rossant1
- 1 Hospital for Sick Children Research Institute;
- 2 Helmholtz Zentrum München;
- 3 HHMI/Children's Hospital Boston;
- 4 Hospital For Sick Children Research Institute;
- 5 Toronto Centre for Phenogenomics
- * Corresponding author; email: b.cox{at}utoronto.ca
Abstract
Mutational screens are an effective means in the functional annotation of the 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 ES cells 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; approximately 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 null mutations can not be responsible for all cases of XLMR.
Footnotes
- Received January 11, 2010.
- Accepted May 11, 2010.
- Copyright © 2010, Cold Spring Harbor Laboratory Press
