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Mutations in Sox18 underlie cardiovascular and hair follicle defects in ragged mice

Nature Genetics volume 24, pages 434437 (2000) | Download Citation



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 factor1, to distal mouse chromosome 2 (ref. 2). This region contains a known mouse mutation, ragged (Ra), that affects the coat and vasculature3,4,5. 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.

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We thank J. Rossant and A. Nagy for the Kdr- and Flt1-mutant embryos and the Kdr riboprobe template; C. Wicking for the Shh and Ptc1 riboprobe templates; and R. Harvey and P. Tam for help in interpreting section data. This work was supported by grants from the National Health and Medical Research Council, Australia, the Australian Research Council (ARC), the National Heart Foundation, Australia and the Medical Research Council, UK.

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  1. Centre for Molecular and Cellular Biology, The University of Queensland, Brisbane, Australia

    • David Pennisi
    • , Jennifer Gardner
    • , Brett Hosking
    • , George Muscat
    •  & Peter Koopman
  2. Human Genetics Unit, Western General Hospital, Edinburgh, UK

    • Doreen Chambers
    •  & Catherine Abbott
  3. MRC Mammalian Genetics Unit, Chilton , Didcot, Oxon., UK

    • Josephine Peters


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Correspondence to Peter Koopman.

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