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Dark skin mutations shed light on inherited anemia

Nature Genetics volume 40, pages 931–932 (2008)Cite this article

A new study of pigmentation in mice has revealed a surprising link between dark skin and defects in ribosomal proteins. The demonstration that this phenotype is mediated via cell-specific stabilization of p53 suggests insights into the pathogenesis of human diseases such as Diamond-Blackfan anemia caused by similar defects in ribosomal proteins.

Children with the human pediatric disease Diamond-Blackfan anemia (DBA) fail to make red blood cells and carry mutations in one copy of any of several genes encoding ribosomal proteins, which are essential components of the protein synthesis machinery1. Haploinsufficiency for individual ribosomal protein genes causing defective ribosome biogenesis is the most likely cause of the disease2. But exactly how abnormal ribosome production leads to a specific failure in one cell type has puzzled scientists ever since the first DBA-causing mutations in RPS19 were reported3. Now, a clue to the mechanism has come from an unlikely source. As reported on page 963 of this issue4, McGowan et al., studying genes associated with pigmentation in mice, have found a connection between mutations in ribosomal protein genes and stabilization of the tumor suppressor p53 that may be important in DBA pathogenesis.

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Figure 1: Mutations in ribosomal protein genes cause dark skin in mice via stabilization of p53.

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  1. Philip J. Mason is in the Departments of Internal Medicine and Genetics, and Monica Bessler is in the Departments of Internal Medicine and Developmental Biology, Washington University School of Medicine, St. Louis, Missouri 63110, USA. pmason@dom.wustl.edu,

    Philip J Mason & Monica Bessler

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  1. Philip J Mason
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  2. Monica Bessler
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Mason, P., Bessler, M. Dark skin mutations shed light on inherited anemia. Nat Genet 40, 931–932 (2008). https://doi.org/10.1038/ng0808-931

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