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

Ribosomal mutations cause p53-mediated dark skin and pleiotropic effects.

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  • 1Department of Genetics, Division of Radiation and CancerBiology, Stanford University, Stanford, California 94305, USA.

Abstract

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.

Comment in

PMID:
18641651
[PubMed - indexed for MEDLINE]
PMCID:
PMC3979291
Free PMC Article

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