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Severe impairment of permatogenesis in mice lacking the CREM gene

Nature volume 380, pages 162–165 (1996)Cite this article

Abstract

SPERMATOGENESIS is a complex developmental process that occurs in several phases. A large number of genes have been identified that are expressed during spermatogenesis1,2, but the biological significance of many of these is not yet known. We have used gene targeting to selectively eliminate the transcription factor CREM (cyclic AMP-responsive element modulator), which is thought to e important for mammalian spermatogenesis3–5. Male mice deficient for all CREM proteins are sterile, as their developing spermatids fail to differentiate into sperm, and postmeiotic gene expression in the testis declines dramatically. The cessation of sperm development is not accompanied by decreases in the levels of follicle-stimulating hormone or testosterone. Our findings indicate that the CREM gene is essential for spermatogenesis, and mice deficient for this transcription factor could serve as a model system for the study of idiopathic infertility in men.

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References

  1. Wolgemuth, D. J. & Watrin, F. Mamm. Genome 1, 283–288 (1991).

    Article  CAS  Google Scholar 

  2. Erikson, R. P. Trends Genet. 6, 264–269 (1990).

    Article  Google Scholar 

  3. Foulkes, N. S., Mellström, B., Benusiglio, E. & Sassone-Corsi, P. Nature 355, 80–84 (1992).

    Article  ADS  CAS  Google Scholar 

  4. Foulkes, N. S., Borreli, E. & Sassone-Corsi, P. Cell 64, 739–749 (1991).

    Article  CAS  Google Scholar 

  5. Foulkes, N. S., Schlotter, F., Pevet, P. & Sassone-Corsi, P. Nature 362, 264–267 (1993).

    Article  ADS  CAS  Google Scholar 

  6. Hurst, H. Protein Profile 2, 105–168 (1995).

    CAS  Google Scholar 

  7. Weinbauer, G. F. & Nieschlag. E. in Molecular Biology of Reproduction (ed. de Kretser, D. M.) 99–142 (Academic, New York, 1993).

    Google Scholar 

  8. Nantel, F. et al. Nature 380, 159–162 (1996).

    Article  ADS  CAS  Google Scholar 

  9. Kashiwabara, S., Arai, Y., Kodaira, K. & Bab, T. Biochem. biophys. Res. Commun. 173, 240–245 (1990).

    Article  CAS  Google Scholar 

  10. Anakwe, O. O., Sharma, S., Hardy, D. M. & Gerton, G. L. Molec. Reprod. Dev. 29, 172–179 (1991).

    Article  CAS  Google Scholar 

  11. Escalier, D. et al. Development 133, 779–788 (1991).

    Google Scholar 

  12. Bellve, A. R. in Oxford Review of Reproductive Biology Vol. 1 (ed. Finne, C. A.) 159–260 (Oxford Univ. Press, 1979).

    Google Scholar 

  13. Kleene, K. C. Development 106, 367–373 (1989).

    CAS  PubMed  Google Scholar 

  14. Heidaran, M. A., Showman, R. M. & Kistler, W. S. J. biol. Chem. 106, 1427–1433 (1988).

    CAS  Google Scholar 

  15. Kleene, K. C. et al. Devl Biol. 137, 395–402 (1990).

    Article  CAS  Google Scholar 

  16. Heidaran, M. A. & Kistler, W. S. Gene 54, 281–284 (1987).

    Article  CAS  Google Scholar 

  17. Zambrowicz, B. P., Harendza, C. J., Zimmermann, J. W., Brinster, R. L. & Palmiter, R. D. Proc. natn. Acad. Sci. U.S.A. 90, 5071–5075 (1993).

    Article  ADS  CAS  Google Scholar 

  18. Kistler, M. K., Sassone-Corsi, P. & Kistler, W. S. Biol. Reprod. 51, 1322–1329 (1994).

    Article  CAS  Google Scholar 

  19. Shin, D. M. & Kleene, K. C. Molec. Reprod. Dev. 33, 222–227 (1992).

    Article  Google Scholar 

  20. Van der Hoorn, F. A. & Tarnasky, H. A. Proc. natn. Acad. Sci. U.S.A. 89, 703–707 (1992).

    Article  ADS  CAS  Google Scholar 

  21. Delmas, V., van der Hoorn, F., Mellström, B., Jegou, B. & Sassone-Corsi, P. Molec. Endocr. 7, 1502–1514 (1993).

    CAS  PubMed  Google Scholar 

  22. Nieschlag, E. Clin. Endocr. 38, 123–133 (1993).

    Article  CAS  Google Scholar 

  23. Chandolia, R. K., Weinbauer, G. F., Simoni, S., Behre, H. M. & Nieschlag, E. Acta endocr. 125, 547–555 (1991).

    Article  CAS  Google Scholar 

  24. Tamura, T. et al. Nucleic Acids Res. 19, 3861–3865 (1991).

    Article  CAS  Google Scholar 

  25. Kaestner, K. H., Montoliu, L., Kern, H., Thulke, M. & Schütz, G. Gene 148, 67–70 (1994).

    Article  CAS  Google Scholar 

  26. Russell, L. D., Ettlin, R. A., Sinha Hikim, A. P. & Clegg, E. D. in Histological and histopathological evaluation of the testis 119–161 (Cache River, Clearwater, FL, 1990).

    Google Scholar 

  27. Klemm, U. et al. Differentiation 42, 160–168 (1990).

    Article  CAS  Google Scholar 

  28. Adham, I. M. et al. DNA Cell Biol. (in the press).

  29. Kleen, K. C., Distel, R. J. & Hecht, N. B. Biochemistry 24, 719–722 (1985).

    Article  Google Scholar 

  30. Kleen, K. C., Borzorgzadeh, A., Flynn, J. F., Yelick, P. C. & Hecht, N. B. Biochim. biophys. Acta 950, 215–220 (1988).

    Article  Google Scholar 

  31. Bibb, M. J., VanEtten, R. A., Wright, C. T., Walberg, M. W. & Clayton, D. A. Cell 26, 167–180 (1981).

    Article  CAS  Google Scholar 

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Author notes

  1. Günther Schütz: To whom correspondence should be addressed.

Authors and Affiliations

  1. Molecular Biology of the Cell I Division, German Cancer Research Center, Neuenheimer Feld 280, D-69120, Heidelberg, Germany

    Julie A. Blendy, Klaus H. Kaestner & Günther Schütz

  2. Institute of Reproductive Medicine of the University, Steinfurterstrasse 107, D-48149, Münster, Germany

    Gerhard F. Weinbauer & Eberhard Nieschlag

Authors
  1. Julie A. Blendy
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  2. Klaus H. Kaestner
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  3. Gerhard F. Weinbauer
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  4. Eberhard Nieschlag
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  5. Günther Schütz
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Blendy, J., Kaestner, K., Weinbauer, G. et al. Severe impairment of permatogenesis in mice lacking the CREM gene. Nature 380, 162–165 (1996). https://doi.org/10.1038/380162a0

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