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Inhibition of skin development by targeted expression of a dominant-negative retinoic acid receptor

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Abstract

ALTHOUGH pharmacological doses of retinoic acid (RA) have a wide variety of actions in vivo1, experimental difficulties have prevented a definitive assignment of its physiological functions. We recently made a dominant-negative retinoic acid receptor (RAR>) by a single amino-acid substitution2 which creates a dominant-negative thyroid hormone receptor3. The mutated RAR efficiently inhibited the endogenous activities of RARs (a, β, y)2. Thus, targeted expression of the mutated receptor should reveal RA functions during organogenesis by blocking RA signalling in the tissues concerned. To address this possibility, we expressed the dominant-negative RAR in the epidermis, a potential target organ of RA4. We report here that the resultant transgenic mice exhibited dramatic suppression of epidermal maturation, demonstrating the requirement of RA in normal skin development.

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References

  1. Armstrong, R. B., Ashenfelter, K. O., Eckhoff, C., Levin, A. A. & Shapiro, S. S. in The Retinoids: Biology, Chemistry, and Medicine 2nd edn (eds Sporn, M. B., Roberts, A. B. & Goodman, D. S.) 545–572 (Raven, New York, 1994).

    Google Scholar 

  2. Saitou, M., Narumiya, S. & Kakizuka, A. J. biol. Chem. 269, 19101–19107 (1994).

    CAS  PubMed  Google Scholar 

  3. Parrilla, R., Mixson, A. J., McPherson, J. A., McClaskey, J. H. & Weintraub, B. D. J. clin. Invest. 88, 2123–2130 (1991).

    Article  CAS  Google Scholar 

  4. Peck, G. L. & DiGiovanna, J. J. in The Retinoids: Biology, Chemistry, and Medicine 2nd edn (eds Sporn, M. B., Roberts, A. B. & Goodman, D. S.) 631–658 (Raven, New York, 1994).

    Google Scholar 

  5. Li, E., Sucov, H. M., Lee, K.-F., Evans, R. M. & Jaenisch, R. Proc. natn. Acad. Sci. U.S.A. 90, 1590–1594 (1993).

    Article  ADS  CAS  Google Scholar 

  6. Lohnes, D. et al. Cell 73, 643–658 (1993).

    Article  CAS  Google Scholar 

  7. Lufkin, T. et al. Proc. natn. Acad. Sci. U.S.A. 90, 7225–7229 (1993).

    Article  ADS  CAS  Google Scholar 

  8. Vassar, R., Rosenberg, M., Ross, S., Tyner, A. & Fuchs, E. Proc. natn. Acad. Sci. U.S.A. 86, 1563–1567 (1989).

    Article  ADS  CAS  Google Scholar 

  9. Byrne, C., Tainsky, M. & Fuchs, E. Development 120, 2369–2383 (1994).

    CAS  PubMed  Google Scholar 

  10. Hanson, J. J. Anat. 81, 174–197 (1947).

    CAS  PubMed  PubMed Central  Google Scholar 

  11. Grüneberg, H. J. Hered. 34, 89–92 (1943).

    Article  Google Scholar 

  12. Fuchs, E. & Green, H. Cell 25, 617–625 (1981).

    Article  CAS  Google Scholar 

  13. Wolbach, S. B. & Howe, P. R. J. exp. Med. 42, 753–777 (1925).

    Article  CAS  Google Scholar 

  14. Dale, B. A., Holbrook, K. A., Kimball, J. R., Hoff, M. & Sun, T.-T. J. Cell Biol. 101, 1257–1269 (1985).

    Article  CAS  Google Scholar 

  15. Weiss, R. A., Eichner, R. & Sun, T.-T. J. Cell Biol. 98, 1397–1406 (1984).

    Article  CAS  Google Scholar 

  16. Kopan, R. & Fuchs, E. J. Cell Biol. 109, 295–307 (1989).

    Article  CAS  Google Scholar 

  17. Fuchs, E. & Green, H. Cell 19, 1033–1042 (1980).

    Article  CAS  Google Scholar 

  18. Hardison, R. C. et al. Cell 18, 1285–1297 (1979).

    Article  CAS  Google Scholar 

  19. Gordon, J. W. in Guide to Techniques in Mouse Development (eds Wassarman, P. M. & DePamphilis, M. L.) 747–771 (Academic, San Diego, 1993).

    Book  Google Scholar 

  20. Sanes, J. R., Rubenstein, J. L. R. & Nicolas, J.-F. EMBO J. 5, 3133–3142 (1986).

    Article  CAS  Google Scholar 

  21. Kakizuka, A. et al. Cell 66, 663–674 (1991).

    Article  CAS  Google Scholar 

  22. Kakizuka, A. et al. Genes Dev. 6, 578–590 (1992).

    Article  CAS  Google Scholar 

  23. Davidson, P. & Hardy, M. H. J. Anat. 86, 342–356 (1952).

    CAS  PubMed  PubMed Central  Google Scholar 

  24. Ivanyi, D. et al. J. Path. 159, 7–12 (1989).

    Article  CAS  Google Scholar 

  25. Stoler, A., Kopan, R., Duvic, M. & Fuchs, E. J. Cell Biol. 107, 427–446 (1988).

    Article  CAS  Google Scholar 

  26. Stoler, A., Duvic, M. & Fuchs, E. J. invest. Dermatol. 93, 728–738 (1989).

    Article  CAS  Google Scholar 

  27. Steinert, P. M. Biochem. J. 149, 39–48 (1975).

    Article  CAS  Google Scholar 

  28. Towbin, H., Staehelin, T. & Gordon, J. Proc. natn. Acad. Sci. U.S.A. 76, 4350–4354 (1979).

    Article  ADS  CAS  Google Scholar 

  29. Ohkubo, H. et al. Proc. natn. Acad. Sci. U.S.A. 87, 5153–5157 (1990).

    Article  ADS  CAS  Google Scholar 

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Authors and Affiliations

  1. Department of Pharmacology, Kyoto University Faculty of Medicine, Kyoto, 606-01, Japan

    Mitinori Saitou, Shuh Narumiya & Akira Kakizuka

  2. Department of Dermatology, Kyoto University Faculty of Medicine, Kyoto, 606-01, Japan

    Toshihiro Tanaka

  3. Fukui Institute for Safety Research, Ono Pharmaceutical, Fukui, 913, Japan

    Satoshi Sugai & Koji Shimouchi

  4. Howard Hughes Medical Institute, Department of Molecular Genetics & Cell Biology, The University of Chicago, Chicago, Illinois, 60637, USA

    Elaine Fuchs

Authors
  1. Mitinori Saitou
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  2. Satoshi Sugai
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  3. Toshihiro Tanaka
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  4. Koji Shimouchi
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  5. Elaine Fuchs
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  6. Shuh Narumiya
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  7. Akira Kakizuka
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Saitou, M., Sugai, S., Tanaka, T. et al. Inhibition of skin development by targeted expression of a dominant-negative retinoic acid receptor. Nature 374, 159–162 (1995). https://doi.org/10.1038/374159a0

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