title: Mutations in Sox18 underlie cardiovascular and hair follicle defects in ragged mice.
abstract: Analysis of classical mouse mutations has been useful in the identification and study of many genes. We previously mapped Sox18, encoding an SRY-related transcription factor, to distal mouse chromosome 2. This region contains a known mouse mutation, ragged (Ra), that affects the coat and vasculature. Here we have directly evaluated Sox18 as a candidate for Ra. We found that Sox18 is expressed in the developing vascular endothelium and hair follicles in mouse embryos. Furthermore, we found no recombination between Sox18 and Ra in an interspecific backcross segregating for the Ra phenotype. We found point mutations in Sox18 in two different Ra alleles that result in missense translation and premature truncation of the encoded protein. Fusion proteins containing these mutations lack the ability to activate transcription relative to wild-type controls in an in vitro assay. Our observations implicate mutations in Sox18 as the underlying cause of the Ra phenotype, and identify Sox18 as a critical gene for cardiovascular and hair follicle formation.
authors.affiliation: Centre for Molecular and Cellular Biology, The University of Queensland, Brisbane, Australia.
authors.forename: D
authors.initials: D
authors.lastname: Pennisi
authors.forename: J
authors.initials: J
authors.lastname: Gardner
authors.forename: D
authors.initials: D
authors.lastname: Chambers
authors.forename: B
authors.initials: B
authors.lastname: Hosking
authors.forename: J
authors.initials: J
authors.lastname: Peters
authors.forename: G
authors.initials: G
authors.lastname: Muscat
authors.forename: C
authors.initials: C
authors.lastname: Abbott
authors.forename: P
authors.initials: P
authors.lastname: Koopman
mesh_terms: D000483:Alleles; D000818:Animals; D018376:Cardiovascular Abnormalities / Q000235:genetics* / Q000473:pathology; D004252:DNA Mutational Analysis; D004730:Endothelium, Vascular / Q000166:cytology / Q000378:metabolism; D018507:Gene Expression Regulation, Developmental; D008040:Genetic Linkage; D018859:Hair Follicle / Q000002:abnormalities* / Q000378:metabolism / Q000473:pathology; D006609:High Mobility Group Proteins / Q000096:biosynthesis / Q000235:genetics*; D017403:In Situ Hybridization; D007178:Inbreeding; D051379:Mice; D008817:Mice, Mutant Strains; D018919:Neovascularization, Physiologic / Q000235:genetics; D010641:Phenotype; D017354:Point Mutation / Q000235:genetics*; D012333:RNA, Messenger / Q000096:biosynthesis; D020794:Receptor Protein-Tyrosine Kinases / Q000096:biosynthesis / Q000172:deficiency / Q000235:genetics; D017978:Receptors, Growth Factor / Q000096:biosynthesis / Q000172:deficiency / Q000235:genetics; D040262:Receptors, Vascular Endothelial Growth Factor; D011995:Recombination, Genetic; D055760:SOXF Transcription Factors; D014157:Transcription Factors / Q000096:biosynthesis / Q000235:genetics*; D015533:Transcriptional Activation
chemical_list: D006609:High Mobility Group Proteins; D012333:RNA, Messenger; D017978:Receptors, Growth Factor; D055760:SOXF Transcription Factors; C490653:Sox18 protein, mouse; D014157:Transcription Factors; D020794:Receptor Protein-Tyrosine Kinases; D040262:Receptors, Vascular Endothelial Growth Factor