Ribosomal mutations cause p53-mediated dark skin and pleiotropic effects

Nat Genet. 2008 Aug;40(8):963-70. doi: 10.1038/ng.188. Epub 2008 Jul 20.


Mutations in genes encoding ribosomal proteins cause the Minute phenotype in Drosophila and mice, and Diamond-Blackfan syndrome in humans. Here we report two mouse dark skin (Dsk) loci caused by mutations in Rps19 (ribosomal protein S19) and Rps20 (ribosomal protein S20). We identify a common pathophysiologic program in which p53 stabilization stimulates Kit ligand expression, and, consequently, epidermal melanocytosis via a paracrine mechanism. Accumulation of p53 also causes reduced body size and erythrocyte count. These results provide a mechanistic explanation for the diverse collection of phenotypes that accompany reduced dosage of genes encoding ribosomal proteins, and have implications for understanding normal human variation and human disease.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Epidermal Cells
  • Epidermis / metabolism
  • Erythrocytes / metabolism
  • Humans
  • Keratinocytes / metabolism
  • Melanocytes / metabolism
  • Mice
  • Mutation
  • Ribosomal Protein S6 / genetics
  • Ribosomal Protein S6 / metabolism
  • Ribosomal Proteins / genetics*
  • Ribosomal Proteins / metabolism
  • Skin Pigmentation*
  • Stem Cell Factor / metabolism
  • Tumor Suppressor Protein p53 / metabolism*


  • Ribosomal Protein S6
  • Ribosomal Proteins
  • Rps19 protein, mouse
  • Stem Cell Factor
  • Tumor Suppressor Protein p53
  • ribosomal protein S19
  • ribosomal protein S20
  • ribosomal protein S6, mouse

Associated data

  • GEO/GSE11331
  • RefSeq/NM_177730