title: Phenotypic annotation of the mouse X chromosome.
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, 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 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/).
authors.affiliation: Program in Developmental and Stem Cell Biology, The Hospital for Sick Children Research Institute, Toronto, Ontario M5G 1L7, Canada.
authors.forename: Brian J
authors.initials: BJ
authors.lastname: Cox
authors.forename: Marion
authors.initials: M
authors.lastname: Vollmer
authors.forename: Owen
authors.initials: O
authors.lastname: Tamplin
authors.forename: Mei
authors.initials: M
authors.lastname: Lu
authors.forename: Steffen
authors.initials: S
authors.lastname: Biechele
authors.forename: Marina
authors.initials: M
authors.lastname: Gertsenstein
authors.forename: Claude
authors.initials: C
authors.lastname: van Campenhout
authors.forename: Thomas
authors.initials: T
authors.lastname: Floss
authors.forename: Ralf
authors.initials: R
authors.lastname: Kühn
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Wurst
authors.forename: Heiko
authors.initials: H
authors.lastname: Lickert
authors.forename: Janet
authors.initials: J
authors.lastname: Rossant
mesh_terms: D000217:Acyltransferases; D000818:Animals; D001483:Base Sequence; D041321:Chromosomes, Human, X / Q000235:genetics; D004252:DNA Mutational Analysis / Q000379:methods*; D005804:Genes, Lethal; D050172:Genes, X-Linked; D040181:Genetic Diseases, X-Linked / Q000235:genetics; D020022:Genetic Predisposition to Disease; D005820:Genetic Testing / Q000379:methods*; D006801:Humans; D008565:Membrane Proteins / Q000235:genetics; D038901:X-Linked Intellectual Disability / Q000235:genetics; D051379:Mice; D058977:Molecular Sequence Annotation; D008969:Molecular Sequence Data; D010641:Phenotype; D011518:Proto-Oncogene Proteins / Q000235:genetics; D012097:Repressor Proteins / Q000235:genetics; D014960:X Chromosome / Q000235:genetics*
chemical_list: C411984:BCOR protein, human; D008565:Membrane Proteins; D011518:Proto-Oncogene Proteins; D012097:Repressor Proteins; D000217:Acyltransferases; C491188:PORCN protein, human