Skip to main content
SpringerLink
Log in

129/Ola mice carrying a null mutation in PrP that abolishes mRNA production are developmentally normal

  • Neurodegenerative Diseases
  • Part II: Transmissible Neurodegenerative Disorders (Proceedings of the symposium “Transmissible and Nontransmissible Neurodegenerative Disorders” held in Ocho Rios, Jamaica, February 28–March 5, 1993)
  • Published:
Molecular Neurobiology Aims and scope Submit manuscript

Abstract

The neural membrane glycoprotein PrP is implicated in the pathogenesis of the transmissible spongiform encephalopathies; however, the normal function of PrP and its precise role in disease are not understood. Recently, gene targeting has been used to produce mice withneo/PrP fusion transcripts, but no detectable PrP protein in the brain (1). Here we report the use of a different targeting strategy, to produce inbred mice with a complete absence of both PrP protein and mRNA sequences. At 7 mo of age, these mice show no overt phenotypic abnormalities despite the normal high levels of expression of PrP during mouse development. The mice are being used in experiments designed to address the role of PrP in the pathogenesis of scrapie and the replication of infectivity.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Bueler H., Fischer M., Lang Y., Bluethmann H., Lipp H.-P., DeArmond S. J., Prusiner S. B., Aguet M., and Weissmann C. (1992)Nature 356, 577–582.

    Article  PubMed  CAS  Google Scholar 

  2. Stahl N., Borchelt D. R., Hsiao K., and Prusiner S. B. (1987)Cell 51, 229–240.

    Article  PubMed  CAS  Google Scholar 

  3. Hope J. and Manson J. (1991) inCurrent Topics in Microbiology and Immunology, vol. 173 (Chesebro B., ed.), Springer Verlag, Heidelberg, pp. 57–74.

    Google Scholar 

  4. Bruce M., McBride P. A., and Farquhar C. F. (1989)Neurosci. Lett. 102, 1–6.

    Article  PubMed  CAS  Google Scholar 

  5. Oesch B., Westaway D., Wälchli M., McKinley M. P., Kent S. B. H., Aebersold R., Barry R. A., Teplow D. B., Tempst D. B., Hood L. E., Prusiner S. B., and Weissman C. (1985)Cell 40, 735–746.

    Article  PubMed  CAS  Google Scholar 

  6. Manson J., McBride P., and Hope J. (1992)Neurodegeneration 1, 45–52.

    Google Scholar 

  7. Westaway D., Goodman P. A., Mirenda C. A., McKinley M. P., Carlson G. A., and Prusiner S. B. (1987)Cell 51 651–662.

    Article  PubMed  CAS  Google Scholar 

  8. Lowenstein D. H., Butler D. A., Westaway D., McKinley M. P., DeArmond S. J., and Prusiner S. B. (1990)Mol. Cell. Biol. 10, 1153–1163.

    PubMed  CAS  Google Scholar 

  9. Goldmann W., Hunter N., Foster J. D., and Hope J. (1991)J. Gen. Virol. 72, 2411–2417.

    PubMed  CAS  Google Scholar 

  10. Doh-ura K., Tateishi J., and Sasaki H. (1989)Biochem. Biophys. Res. Commun. 163, 974–979.

    Article  PubMed  CAS  Google Scholar 

  11. Collinge J., Harding A. E., Owen F., Poulter M., Lofthouse R., Boughhey A. M., Shah T., and Crow T. J. (1989)Lancet ii, 15–17.

    Article  Google Scholar 

  12. Owen F., Poulter M., Shah T., Collinge J., Lofthouse R., Baker H., Ridley R., McVey J., and Crow T. J. (1990)Molec. Brain Res. 7, 273–276.

    Article  PubMed  CAS  Google Scholar 

  13. Scott M., Foster D., Mirenda C., Serban D., Coufal F., Wälchli M., Torchia M., Groth D., Carlson G. A., DeArmond S. J., Westaway D., and Prusiner S. B. (1989)Cell 59, 847–857.

    Article  PubMed  CAS  Google Scholar 

  14. Westaway D., Mirenda C. A., Foster D., Zebarjadian Y., Scott M., Torchia M., Yang S.-L., Serbal H., DeArmond S. J., Ebeling C., Prusiner S. B., and Carlson G. A. (1991)Neuron 7, 59–68.

    Article  PubMed  CAS  Google Scholar 

  15. Hsiao K. K., Scott M., Foster D., Groth D. F., DeArmond S. J., and Prusiner S. B. (1990)Science 250, 1587–1590.

    Article  PubMed  CAS  Google Scholar 

  16. Kretschmar H. A., Prusiner S. B., Stowring L. E., and DeArmond S. J. (1986)Am. J. Pathol. 122, 1–5.

    Google Scholar 

  17. Manson J., West J. D., Thomson V., McBride P., Kaufman M. H., and Hope J. (1992)Development 115, 117–122.

    PubMed  CAS  Google Scholar 

  18. Hooper M. L., Hardy K., Handyside A., Hunter S., and Monk M. (1987)Nature 326, 292–295.

    Article  PubMed  CAS  Google Scholar 

  19. Handyside A. H., O'Neill G. T., Jones M., and Hooper M. L. (1989)Roux's Arch. Dev. Biol. 198, 48–55.

    Article  Google Scholar 

  20. Chomczynski P. and Sacchi N. (1987)Anal. Biochem. 162, 156–159.

    Article  PubMed  CAS  Google Scholar 

  21. Dodd P. R., Hardy J. A., Oakley A. E., Edwardson J. A., Perry E. K., and Delaunoy J. P. (1981)Brain Res. 226, 107–115.

    Article  PubMed  CAS  Google Scholar 

  22. Farquhar C. F., Somerville R. A., and Ritchie L. A. (1989)J. Virol. Met. 24, 215–222.

    Article  CAS  Google Scholar 

  23. Thomas K. R. and Capecchi M. R. (1987)Cell 51, 503–512.

    Article  PubMed  CAS  Google Scholar 

  24. Colbere-Garapin F., Chousterman S., Horodniceanu F., Kourilsky P., and Garapin A.-C. (1979)Proc. Natl. Acad. Sci. USA 76, 3755–3759.

    Article  PubMed  CAS  Google Scholar 

  25. Ramirez-Solis R., Zheng H., Whiting J., Krumlauf R., and Bradley A. (1993)Cell 73, 279–294.

    Article  PubMed  CAS  Google Scholar 

  26. Su L. K., Kinzler K., Vogelstein B., Preisinger A. C., Moser A. R., Luongo C., Gould K. A., and Dove W. F. (1992)Science 256, 668–670.

    Article  PubMed  CAS  Google Scholar 

  27. Moser A. R., Pitot H. C., and Dove W. F. (1990)Science 247, 323–324.

    Article  Google Scholar 

  28. Donehower L. A., Harvey M., Slagle B. L., McArthur M. J., Montgomery C. A., Butel J. S., and Bradley A. (1992)Nature 356, 215–221.

    Article  PubMed  CAS  Google Scholar 

  29. Zijlstra M., Bik M., Simister M. E., Loring J. M., Raulet D. H., and Jaenisch R. (1990)Nature 344, 742–746.

    Article  PubMed  CAS  Google Scholar 

  30. Kingsley D. M., Rinchik E. M., Russell L. B., Ottiger H.-P., Sutcliffe J. G., Copeland N. G., and Jenkins N. A. (1990)EMBO J. 9, 395–399.

    PubMed  CAS  Google Scholar 

  31. Dickinson A. G., Meikle V. M., and Fraser H. (1968)J. Comp. Path. 78, 293–299.

    Article  PubMed  CAS  Google Scholar 

  32. Carlson G. A., Kingsbury D. T., Goodman P. A., Coleman S., Marshall S. T., DeArmond S., Westaway D., and Prusiner S. B. (1986)Cell 46, 503–511.

    Article  PubMed  CAS  Google Scholar 

  33. Hunter N., Hope J., McConnell I., and Dickinson A. G. (1987)J. Gen. Virol. 68, 2711, 2712.

    Article  PubMed  CAS  Google Scholar 

  34. Goldfarb L. G., Haltia M., Brown P., Nieto A., Kovanen J., McCombie W. R., Trapp S., and Gajdusek D. C. (1991)Lancet 337, 425.

    Article  PubMed  CAS  Google Scholar 

  35. Hsiao K., Dlouhy S. R., Farlow M. R., Cass C., Costa M. D., Conneally P. M., Hodes M. E., Ghetti B., and Prusiner S. B. (1992)Nature Genet. 1, 68–71.

    Article  PubMed  CAS  Google Scholar 

  36. Kitamoto T., Ohta M., Doh-ura K., Hitoshi S., Terao Y., and Tateishi J. (1993)Biochem. Biophys. Res. Commun. 191, 709–714.

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Institute for Animal Health, AFRC and MRC Neuropathogenesis Unit, Ogston Building, West Mains Road, EH9 3JF, Edinburgh

    J. C. Manson, L. Aitchison, I. McConnell & J. Hope

  2. CRC Laboratories, Department of Pathology, University of Edinburgh, Edinburgh, UK

    A. R. Clarke & M. L. Hooper

Authors
  1. J. C. Manson
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. A. R. Clarke
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. M. L. Hooper
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. L. Aitchison
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. I. McConnell
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. J. Hope
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

About this article

Cite this article

Manson, J.C., Clarke, A.R., Hooper, M.L. et al. 129/Ola mice carrying a null mutation in PrP that abolishes mRNA production are developmentally normal. Mol Neurobiol 8, 121–127 (1994). https://doi.org/10.1007/BF02780662

Download citation

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF02780662

Index Entries

Search

Navigation