R-spondin1 is essential in sex determination, skin differentiation and malignancy

Nat Genet. 2006 Nov;38(11):1304-9. doi: 10.1038/ng1907. Epub 2006 Oct 15.


R-spondins are a recently characterized small family of growth factors. Here we show that human R-spondin1 (RSPO1) is the gene disrupted in a recessive syndrome characterized by XX sex reversal, palmoplantar hyperkeratosis and predisposition to squamous cell carcinoma of the skin. Our data show, for the first time, that disruption of a single gene can lead to complete female-to-male sex reversal in the absence of the testis-determining gene, SRY.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Carcinoma, Squamous Cell / genetics
  • Cell Differentiation / genetics*
  • Cells, Cultured
  • Chromosome Aberrations
  • DNA Mutational Analysis
  • Disorders of Sex Development
  • Female
  • Genetic Predisposition to Disease*
  • Humans
  • Keratoderma, Palmoplantar / genetics
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mice, Inbred CBA
  • Mutation
  • Pedigree
  • Sex Determination Processes*
  • Skin / cytology*
  • Skin / embryology
  • Skin Neoplasms / genetics*
  • Thrombospondins / genetics*
  • Thrombospondins / physiology*


  • RSPO1 protein, human
  • Thrombospondins