Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

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.

This is a preview of subscription content, access via your institution

Access options

Buy article

Get time limited or full article access on ReadCube.

$32.00

Buy

All prices are NET prices.

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

References

  1. Ellis, S.R. & Lipton, J.M. Curr. Top. Dev. Biol. 82, 217–241 (2008).

    Article  CAS  PubMed  Google Scholar 

  2. Gazda, H.T. et al. Br. J. Haematol. 127, 105–113 (2004).

    Article  CAS  PubMed  Google Scholar 

  3. Draptchinskaia, N. et al. Nat. Genet. 21, 169–175 (1999).

    Article  CAS  PubMed  Google Scholar 

  4. McGowan, K.A. et al. Nat. Genet. 40, 963–970 (2008).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. Volarevic, S. et al. Science 288, 2045–2047 (2000).

    Article  CAS  Google Scholar 

  6. Panic, L., Montagne, J., Cokaric, M. & Volarevic, S. Cell Cycle 6, 20–24 (2007).

    Article  CAS  Google Scholar 

  7. Wehrle-Haller, B. Pigment Cell Res. 16, 287–296 (2003).

    Article  CAS  PubMed  Google Scholar 

  8. Perdahl, E.B., Naprstek, B.L., Wallace, W.C. & Lipton, J.M. Blood 83, 645–650 (1994).

    CAS  PubMed  Google Scholar 

  9. Miyake, K. et al. Stem Cells 26, 323–329 (2008).

    Article  CAS  PubMed  Google Scholar 

  10. Danilova, N., Sakamota, K.M. & Lin, S. Blood advance online publication, 10.1182/blood-2008-01-132290 (30 May 2008).

  11. Jones, N.C. et al. Nat. Med. 14, 125–133 (2008).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Kennedy, R.D. & D'Andrea, A.D. Genes Dev. 19, 2925–2940 (2005).

    Article  CAS  PubMed  Google Scholar 

  13. Ogden, G.R., Lane, D.P. & Chisholm, D.M. J. Clin. Pathol. 46, 169–170 (1993).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Artandi, S.E. & Attardi, L.D. Biochem. Biophys. Res. Commun. 331, 881–890 (2005).

    Article  CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  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

Authors
  1. Philip J Mason
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Monica Bessler
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and Permissions

About this article

Cite this article

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

Download citation

  • Issue Date:

  • DOI: https://doi.org/10.1038/ng0808-931

Search

Advanced search

Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing