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.

  • Letter
  • Published:

Testicular degeneration in Bclw-deficient mice

Nature Genetics volume 18, pages 251–256 (1998)Cite this article

Abstract

To identify genes required for mammalian spermatogenesis, we screened lines of mutant mice created using a retroviral genetrap system1 for male infertility. Homozygous ROSA41 male mice exhibit sterility associated with progressive testicular degeneration. Germ-cell defects are first observed at 19 days post-natal (p19). Spermatogenesis is blocked during late spermiogenesis in young adults. Gradual depletion of all stages of germ cells results in a Sertoli-cell-only phenotype by approximately six months of age. Subsequently, almost all Sertoli cells are lost from the seminiferous tubules and the Leydig cell population is reduced. Molecular analysis indicates that the gene mutated is Bclw, a death-protecting member of the Bcl2 family. The mutant allele of Bclw in ROSA41 does not produce a Bclw polypeptide. Expression of Bclw in the testis appears to be restricted to elongating spermatids and Sertoli cells. Potential roles for Bclw in testicular function are discussed.

Access through your institution
Buy or subscribe

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

Access options

Access through your institution

Buy this article

  • Purchase on SpringerLink
  • Instant access to full article PDF
Buy now

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

Similar content being viewed by others

References

  1. Friedrich, G. & Soriano, P. Promoter traps in embryonic stem cells: a genetic screen to identify and mutate developmental genes in mice. Genes Dev. 5, 1513–1523 (1991).

    Article  CAS  Google Scholar 

  2. Gibson, L. et al. bcl-w, a novel member of the bcl-2 family, promotes cell survival. Oncogene 13, 665–675 (1996).

    CAS  PubMed  Google Scholar 

  3. Townley, D.J., Avery, B.J., Rosen, B. & Skarnes, W.C. Rapid sequence analysis of gene trap integrations to generate a resource of insertional mutations in mice. Genome Res. 7, 293–298 (1997).

    Article  CAS  Google Scholar 

  4. Enders, G.C. & May, J.J. Developmentally regulated expression of a mouse germ cell nuclear antigen examined from embryonic day 11 to adult in male and female. Dev. Biol. 163, 331–340 (1994).

    Article  CAS  Google Scholar 

  5. Hall, P.A. et al. Proliferating cell nuclear antigen (PCNA) immunolocalization in paraffin sections : an index of cell proliferation with evidence of deregulated expression in some neoplasms. J. Pathol. 162, 285–294 (1990).

    Article  CAS  Google Scholar 

  6. Russell, L.D. & Griswold, M.D. The Sertoli Cell. (Cache River Press, Clearwater, Florida, 1993).

    Google Scholar 

  7. Mori, C. et al. Morphological analysis of germ cell apoptosis during postnatal testis development in normal and Hsp 70-2 knockout mice. Dev. Dynamic. 208, 125–136 (1997).

    Article  CAS  Google Scholar 

  8. Huckins, C. The morphology and kinetics of spermatogonial degeneration in normal adult rats : An analysis using a simplified classification of germinal epithelium. Anat Rec. 190, 905–926 (1978).

    Article  CAS  Google Scholar 

  9. Korsmeyer, S.J. Regulators of cell death. Trends Genet. 11, 101–105 (1995).

    Article  CAS  Google Scholar 

  10. Furuchi, T., Masuko, K., Nishimune, Y., Obinata, M. & Matsui, Y. Inhibition of testicular germ cell apoptosis and differentiation in mice misexpressing Bcl-2 in spermatogonia. Development 122, 1703–1709 (1996).

    CAS  PubMed  Google Scholar 

  11. Knudson, C.M., Tung, K.S., Tourtellotte, W.G., Brown, G.A. & Korsmeyer, S.J. Bax-deficient mice with lymphoid hyperplasia and male germ cell death. Science 270, 96–99 (1995).

    Article  CAS  Google Scholar 

  12. Vergouwen, R.P.F.A., Jacobs, S.G.P.M., Huiskamp, R., Davids, J.A.G. & de Rooij, D.G. Proliferative activity of gonocytes, Sertoli cells and interstitial cells during testicular development in mice. J. Reprod. Pert. 93, 233–243 (1991).

    Article  CAS  Google Scholar 

  13. Farrow, S.N. et al. Cloning of a bcl-2 homologue by interaction with adenovirus E1B 19K. Nature 374, 731–733 (1995).

    Article  CAS  Google Scholar 

  14. Skinner, M.K. in The Sertoli cell. (eds Russell, L.D. & Griswold, M.D.) 237–247 (Cache River Press, Clearwater, Florida, 1993).

    Google Scholar 

  15. Xia, Z., Dickens, M., Raingeaud, J., Davis, R.J. & Greenberg, M.E. Opposing effects of ERK and JNK-p38 MAP kinases on apoptosis. Science 270, 1326–1331 (1995).

    Article  CAS  Google Scholar 

  16. Dudek, H. et al. Regulation of neuronal survival by the serine-threonine protein kinase Akt. Science 275, 661–665 (1997).

    Article  CAS  Google Scholar 

  17. Cailleau, J., Vermeire, S. & Verhoeven, G. Independent control of the production of insulin-like growth factor I and its binding protein by cultured testicular cells. Mol. Cell. Endocrinol. 69, 79–89 (1990).

    Article  CAS  Google Scholar 

  18. Ayer-LeLiviere, C., Olson, L., Ebendal, T., Hallbrook, F. & Persson, H. Nerve growth factor mRNA and protein in the testis and epididymis of mouse and rat. Proc. Natl. Acad. Sci. USA 85, 2628–2632 (1988).

    Article  Google Scholar 

  19. Dirami, G., Ravindranath, N., Kleinman, H.K. & Dym, M. Evidence that basement membrane prevents apoptosis of Sertoli cells in vitro in the absence of known regulators of Sertoli cell function. Endocrinology 136, 4439–4447 (1995).

    Article  CAS  Google Scholar 

  20. Sharpe, R.M. in The Sertoli cell (eds Russell, L.D. & Skinner, M.K.) 391–418 (Cache River Press, Clearwater, Florida, 1993).

    Google Scholar 

  21. MacGregor, G.R. & Caskey, C.T. Construction of plasmids that express E. coli beta-galactosidase in mammalian cells. Nucleic Acids Res. 17, 2365 (1989).

  22. Ausubel, F.M. et al. Current Protocols in Molecular Biology. (Wiley Interscience, New York, 1994).

    Google Scholar 

  23. Rowe, L.B. et al. Maps from two interspecific backcross DNA panels available as a community genetic mapping resource. Mamm. Genome 5, 253–274 (1994).

    Article  CAS  Google Scholar 

  24. Chaudhary, J., Cupp, A.S. & Skinner, M.K. Role of basic-helix-loop-helix transcription factors in Sertoli cell differentiation: identification of an E-box response element in the transferrin promoter. Endocrinology 138, 667–675 (1997).

    Article  CAS  Google Scholar 

  25. MacGregor, G.R., Zambrowicz, B.P. & Soriano, P. Tissue non-specific alkaline phosphatase is expressed in both embryonic and extra-embryonic lineages during mouse embryogenesis but is not required for migration of primordial germ cells. Development 121, 1487–1496 (1995).

    CAS  Google Scholar 

  26. Sprando, R.L. in Histopathological Evaluation of the Testis. (eds Russell, L.D., Ettlin, R.A., Sinha Hikim, A.P. & Clegg, E.D.) 277–280 (Cache River Press, Clearwater, Florida, 1990).

    Google Scholar 

  27. Russell, L.D. & Burguet, S. Ultrastructure of Leydig cells as revealed by secondary treatment with a ferrocyanide-osmium mixture. Tissue Cell. 9, 751–766 (1977).

    Article  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Center for Molecular Medicine, Emory University School of Medicine, 1462 Clifton Rd. NE, Atlanta, Georgia, 30322, USA

    Andrea J. Ross, Katrina G. Waymire & Grant R. MacGregor

  2. BBSRC Center for Genome Research, University of Edinburgh, Kings Buildings, Edinburgh, EH9 3JQ, UK

    Julie E. Moss

  3. Harbor-UCLA Medical Center, 1000 West Carson Street, Torrance, California, 90509, USA

    A.F. Parlow

  4. Center for Reproductive Biology, Department of Genetics and Cell Biology, Washington State University, Pullman, Washington, 99164, USA

    Michael K. Skinner

  5. Dept. of Physiology, Southern Illinois University School of Medicine, Carbondale, Illinois, 62901, USA

    Lonnie D. Russell

Authors
  1. Andrea J. Ross
    View author publications

    You can also search for this author inPubMed Google Scholar

  2. Katrina G. Waymire
    View author publications

    You can also search for this author inPubMed Google Scholar

  3. Julie E. Moss
    View author publications

    You can also search for this author inPubMed Google Scholar

  4. A.F. Parlow
    View author publications

    You can also search for this author inPubMed Google Scholar

  5. Michael K. Skinner
    View author publications

    You can also search for this author inPubMed Google Scholar

  6. Lonnie D. Russell
    View author publications

    You can also search for this author inPubMed Google Scholar

  7. Grant R. MacGregor
    View author publications

    You can also search for this author inPubMed Google Scholar

Corresponding author

Correspondence to Grant R. MacGregor.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Ross, A., Waymire, K., Moss, J. et al. Testicular degeneration in Bclw-deficient mice. Nat Genet 18, 251–256 (1998). https://doi.org/10.1038/ng0398-251

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1038/ng0398-251

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