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Synpolydactyly in mice with a targeted deficiency in the HoxD complex

Abstract

THE morphogenesis of mammalian digits requires the function of several genes of the HoxD complex during development of limb buds1–4. Using embryonic stem (ES) cells and a site-specific recombination system (loxP/Cre), we have induced a deficiency5,6 that eliminates the products of the Hoxd-13, Hoxd-12 and Hoxd-11 genes simultaneously. A Hoxd-11/lacz reporter gene replaced the deleted region in order to monitor the effect of this triple inactivation at the cellular level. Mice homozygous for this deficiency showed small digit primordia, a disorganized cartilage pattern and impaired skeletal mass. These alterations are similar to the defects seen in a human synpolydactyly7,8, suggesting that this syndrome, which is associated with a subtle mutation in HOXD13 (ref. 8), may involve the loss of function of several Hoxd genes. These results indicate the existence of a functional hierarchy among these genes and provide us with an animal model to study human digit malformations.

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References

  1. Dollé, P. et al. Cell 75, 431–441 (1993).

    Article  Google Scholar 

  2. Sordino, P. F., van der Hoeven, F. & Duboule, D. Nature 375, 678–681 (1995).

    Article  ADS  CAS  Google Scholar 

  3. Davis, A. P. & Capecchi, M. R. Development 122, 1175–1185 (1996).

    CAS  PubMed  Google Scholar 

  4. Nelson et al. Development 122, 1449–1466 (1996).

    CAS  PubMed  Google Scholar 

  5. Gu, H., Zhou, Y. R. & Rajewsky, K. Cell 73, 1155–1164 (1993).

    Article  CAS  Google Scholar 

  6. Ramirez-Solis, R., Liu, P. & Bradley, A. Nature 378, 720–724 (1995).

    Article  ADS  CAS  Google Scholar 

  7. Akarsu, A. N. et al. Med. Genet. 32, 435–441 (1995).

    Article  CAS  Google Scholar 

  8. Muragaki, Y. et al. Science 272, 548–551 (1996).

    Article  ADS  CAS  Google Scholar 

  9. Krumlauf, R. Cell 78, 191–201 (1994).

    Article  CAS  Google Scholar 

  10. van der Hoeven, F., Zákány, J. & Duboule, D. Cell 85, 1025–1035 (1996).

    Article  CAS  Google Scholar 

  11. Izpisúa-Belmonte, J.-C. et al. EMBO J. 10, 2279–2289 (1991).

    Article  Google Scholar 

  12. Kondo, T. et al. Development (in the press).

  13. Favier, B. et al. Proc. Natl Acad. Sci. USA 92, 310–314 (1995).

    Article  ADS  CAS  Google Scholar 

  14. Davis, A. P. & Capecchi, M. R. Development 120, 2187–2198 (1994).

    CAS  Google Scholar 

  15. Sarfarazi, M., Akarsu, A. N. & Sayli, B. S. Hum. Mol. Genet. 4, 1453–1458 (1995).

    Article  CAS  Google Scholar 

  16. Duboule, D. & Morata, G. Trends Genet. 10, 358–364 (1994).

    Article  CAS  Google Scholar 

  17. Forrest, D. et al. EMBO J. 15, 3006–3015 (1996).

    Article  CAS  Google Scholar 

Download references

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Zákány, J., Duboule, D. Synpolydactyly in mice with a targeted deficiency in the HoxD complex. Nature 384, 69–71 (1996). https://doi.org/10.1038/384069a0

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