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.

  • Correspondence
  • Published:

Late onset of renal and hepatic cysts in Pkd1-targeted heterozygotes

Nature Genetics volume 21, pages 160–161 (1999)Cite this article

Autosomal dominant polycystic kidney disease (ADPKD) due to PKD1 mutations is characterized by the progressive appearance of renal, hepatic and pancreatic cysts in adults1. We previously reported that targeted deletion of exon 34 in Pkd1, the mouse homologue of PKD1 , results in renal cysts and perinatal death in homozygotes2. Here we report that Pkd1+/- mice progressively develop scattered renal and hepatic cysts.

Serial sections of 15 Pkd1+/- mice of 9-14 months of age revealed 1-7 renal cysts (of more than 5 times the normal tubule diameter) per animal in 12 mice (80%), of which 5 mice had bilateral cysts. After 16 months, 2-50 cysts were found in all 8 mice examined (100%, Table 1) and 6 of 8 mice had bilateral cysts. Renal excretory function (serum creatinine) was normal in all but one mouse with extensive disease. There were no cysts in five, age-matched, control littermates.

Table 1 Number of renal cysts and liver function in Pkd1+/- mice
Full size table

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

Relevant articles

Open Access articles citing this article.

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Figure 1: Kidney and liver cysts in Pkd1+/- mice.

References

  1. Gabow, P.A. N. Engl. J. Med. 329, 332–342 (1993).

    Article  CAS  Google Scholar 

  2. Lu, W. et al. Nature Genet. 17, 179–181 (1997).

    Article  CAS  Google Scholar 

  3. Orellana, S.A., Sweeney, W.E., Neff, C.D. & Avner, E.D. Kidney Int. 47, 490–499 (1995).

    Article  CAS  Google Scholar 

  4. Ward, C.J. et al. Proc. Natl Acad. Sci. USA 93, 1524– 1528 (1996).

    Article  CAS  Google Scholar 

  5. Geng, L. et al. J. Clin. Invest. 98, 2674– 2682 (1996).

    Article  CAS  Google Scholar 

  6. Everson, G.T. Am. J. Kidney. Dis. 22, 520–525 (1993).

    Article  CAS  Google Scholar 

  7. Patterson, M., Gonzalez–Vitale, J.C. & Fagan, C.J. Hepatology 2, 475–478 (1982).

    Article  CAS  Google Scholar 

  8. Everson, G.T., Emmett, M., Brown, W.R., Redmond, P. & Thickman, D. Hepatology 11, 557– 565 (1990).

    Article  CAS  Google Scholar 

  9. Ramos, A. et al. Arch. Pathol. Lab. Med. 114, 180– 184 (1990).

    CAS  PubMed  Google Scholar 

  10. Fick, G.M. et al. J. Am. Soc. Nephrol. 4, 1654– 1660 (1994).

    CAS  PubMed  Google Scholar 

  11. Gabow, P.A. & Grantham, J.J. in Disease of Kidney (eds Schrier, R.W. & Gottschalk, C.W.) 521–560 (Little Brown, Boston, 1997).

    Google Scholar 

  12. Reeders, S.T. Nature Genet. 1, 235–237 (1992).

    Article  CAS  Google Scholar 

  13. Qian, F., Watnick, T.J., Onuchic, L.F. & Germino, G.G. Cell 87, 979–987 ( 1996).

    Article  CAS  Google Scholar 

  14. Brasier, J.L. & Henske, E.P. J. Clin. Invest. 99 , 194–199 (1997).

    Article  CAS  Google Scholar 

  15. Wu, G. et al. Cell 93, 177–188 (1998).

    Article  CAS  Google Scholar 

Download references

Acknowledgements

We thank H. You and J. Edwards for technical assistance and S.T. Reeders and Y. Segal for discussions. This work was supported by the National Institutes of Health grants DK 40703 to S.T.R. and DK 51050 to J.Z., and the Polycystic Kidney Research Foundation.

Author information

Authors and Affiliations

  1. Renal Division, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, 02115, Massachusetts

    Weining Lu, Xiaohong Fan, Nuria Basora, Hermik Babakhanlou & Jing Zhou

  2. Department of Pathology, Brigham and Women's Hospital, Harvard Medical School, Boston, 02115, Massachusetts

    Helmut G. Rennke

  3. Department of Laboratory Medicine, Children's Hospital, Harvard Medical School, Boston, 02115, Massachusetts

    Terry Law & Nader Rifai

  4. Department of Pathology, Children's Hospital, Harvard Medical School, Boston, 02115 , Massachusetts

    Antonio R. Perez-Atayde

  5. MRC Molecular Haematology Unit, John Radcliffe Hospital , Oxford, Headington, UK

    Peter C. Harris

Authors
  1. Weining Lu
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Xiaohong Fan
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Nuria Basora
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Hermik Babakhanlou
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Terry Law
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Nader Rifai
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Peter C. Harris
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Antonio R. Perez-Atayde
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Helmut G. Rennke
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Jing Zhou
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Jing Zhou.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Lu, W., Fan, X., Basora, N. et al. Late onset of renal and hepatic cysts in Pkd1-targeted heterozygotes . Nat Genet 21, 160–161 (1999). https://doi.org/10.1038/5944

Download citation

  • Issue Date:

  • DOI: https://doi.org/10.1038/5944

This article is cited by

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