1887

Abstract

Expression of the cellular prion protein PrP is for the development of transmissible spongiform encephalopathy and thus for the accumulation of the illness-associated conformer PrP. Therefore, the tissue distribution of PrP at the protein level in both quantitative and qualitative terms was investigated. PrP was quantified using a two-site enzyme immunometric assay which was calibrated with purified ovine recombinant prion protein (rPrP). The most PrP-rich tissue was the brain, followed by the lungs, skeletal muscle, heart, uterus, thymus and tongue, which contained between 20- and 50-fold less PrP than the brain. The PrP content of these tissues seems to be comparable between sheep. Other organs, however, showed different, but low, levels of the protein depending on the animal examined. This was also the case for tissues from the gastrointestinal tract. The tissue containing the lowest concentration of PrP was shown to be the liver, where PrP was found to be between 564- and 16000-fold less abundant than in the brain. PrP was concentrated from crude cellular extracts by immunoprecipitation using several monoclonal and polyclonal anti-ovine PrP antibodies. Interestingly, it was observed that the isoform profile of PrP was tissue-specific. The most atypical electrophoretic profile of PrP was found in the skeletal muscle, where two polypeptides of 32 and 35 kDa were detected.

Loading

Article metrics loading...

/content/journal/jgv/10.1099/0022-1317-82-8-2017
2001-08-01
2020-07-06
Loading full text...

Full text loading...

/deliver/fulltext/jgv/82/8/0822017a.html?itemId=/content/journal/jgv/10.1099/0022-1317-82-8-2017&mimeType=html&fmt=ahah

References

  1. Andréoletti O., Berthon P., Marc D., Sarradin P., Grosclaude J., van Keulen L., Schelcher F., Elsen J.-M., Lantier F.. 2000; Early accumulation of PrPSc in gut-associated lymphoid and nervous tissues of susceptible sheep from a Romanov flock with natural scrapie. Journal of General Virology81:3115–3126
    [Google Scholar]
  2. Antoine N., Cesbron J. Y., Coumans B., Jolois O., Zorzi W., Heinen E.. 2000; Differential expression of cellular prion protein on human blood and tonsil lymphocytes. Haematologica85:475–480
    [Google Scholar]
  3. Askanas V., Bilak M., Engel W. K., Alvarez R. B., Tomé F., Leclerc A.. 1993; Prion protein is abnormally accumulated in inclusion body myositis. Neurology Report5:25–28
    [Google Scholar]
  4. Beekes M., McBride P. A.. 2000; Early accumulation of pathological PrP in the enteric nervous system and gut-associated lymphoid tissue of hamsters orally infected with scrapie. Neuroscience Letters278:181–184
    [Google Scholar]
  5. Bendheim P. E., Brown H. R., Rudelli R. D., Scala L. J., Goller N. L., Wen G. Y., Kascsak R. J., Cashman N. R., Bolton D. C.. 1992; Nearly ubiquitous tissue distribution of the scrapie agent precursor protein. Neurology42:149–156
    [Google Scholar]
  6. Bons N., Mestre-Rances N., Belli P., Cathala F., Gajdusek D. C., Brown P.. 1999; Natural and experimental infection of nonhuman primates by bovine spongiform encephalopathy agents. Proceedings of the National Academy of Sciences, USA96:4046–4051
    [Google Scholar]
  7. Bossers A., Schreuder B. E. C., Muileman I. H., Belt P. B. G. M., Smith M. A.. 1996; PrP genotypes contribute to determining survival times of sheep with natural scrapie. Journal of General Virology77:2669–2673
    [Google Scholar]
  8. Brown D. R., Schmidt B., Groschup M. H., Kretzschmar H. A.. 1998; Prion protein expression in muscle cells and toxicity of a prion protein fragment. European Journal of Cell Biology75:29–37
    [Google Scholar]
  9. Büeler H. R., Aguzzi A., Sailer A., Greiner R. A., Autenried P., Aguet M., Weissmann C.. 1993; Mice devoid of PrP are resistant to scrapie. Cell73:1339–1347
    [Google Scholar]
  10. Cashman N. R., Loertscher R., Nalbantoglu J., Shaw I., Kascsak R. J., Bolton D. C., Bendheim P. E.. 1990; Cellular isoform of the scrapie agent protein participates in lymphocyte activation. Cell61:185–192
    [Google Scholar]
  11. Danner K.. 1993; BSE: a risk for man through pharmaceutical products? Position and politics of the German pharmaceutical industry. In Transmissible Spongiform Encephalopathies: Impact on Animal and Human Health pp199–205 Edited by Brown F. Basel: Karger;
    [Google Scholar]
  12. DeArmond S. J., Qiu Y., Sanchez H., Spilman P. R., Ninchak-Casey A., Alonso D., Daggett V.. 1999; PrPC glycoform heterogeneity as a function of brain region: implications for selective targeting of neurons by prion strains. Journal of Neuropathology and Experimental Neurology58:1000–1009
    [Google Scholar]
  13. Ellman G., Courteney K., Andres V., Featherstone R.. 1961; A new and rapid colorimetric determination of acetylcholinesterase activity. Biochemical Pharmacology7:88–95
    [Google Scholar]
  14. Elsen J. M., Amigues Y., Schelcher F., Ducrocq V., Andréoletti O., Eychenne F., Khang J. V., Poivey J. P., Lantier F., Laplanche J. L.. 1999; Genetic susceptibility and transmission factors in scrapie: detailed analysis of an epidemic in a closed flock of Romanov. Archives of Virology144:431–445
    [Google Scholar]
  15. Gohel C., Grigoriev V., Escaig-Haye F., Lasmezas C. I., Deslys J. P., Langeveld J., Akaaboune M., Hantai D., Fournier J. G.. 1999; Ultrastructural localization of cellular prion protein (PrPC) at the neuromuscular junction. Journal of Neuroscience Research55:261–267
    [Google Scholar]
  16. Goldmann W., O’Neill G., Cheung F., Charleson F., Hunter N.. 1999; PrP (prion) gene expression in sheep may be modulated by alternative polyadenylation of its messenger RNA. Journal of General Virology80:2275–2283
    [Google Scholar]
  17. Grassi J., Frobert Y., Lamourette P., Lagoutte B.. 1988; Screening of monoclonal antibodies using antigen labeled with acetylcholinesterase: applications to the peripheral proteins photosystem I. Analytical Biochemistry168:436–450
    [Google Scholar]
  18. Hadlow W. J., Kennedy R. C., Race R. E.. 1979; Natural infection of Suffolk sheep with scrapie virus. Journal of Infectious Diseases146:657–664
    [Google Scholar]
  19. Horiuchi M., Yamazaki N., Ikeda T., Ishiguro N., Shinagawa M.. 1995; A cellular form of prion protein (PrPC) exists in many non-neuronal tissues of sheep. Journal of General Virology76:2583–2587
    [Google Scholar]
  20. Hunter N., Foster J. D., Goldmann W., Stear M. J., Hope J., Bostock C.. 1996; Natural scrapie in closed flock of Cheviot sheep occurs only in specific PrP genotypes. Archives of Virology141:809–824
    [Google Scholar]
  21. Jackson G. S., Clarke A. R.. 2000; Mammalian prion proteins. Current Opinion in Structural Biology10:69–74
    [Google Scholar]
  22. Krasemann S., Groschup M. H., Haremeyer S., Hunsmann G., Bodemer W.. 1996; Generation of monoclonal antibodies against human prion proteins in PrP0/0 mice. Molecular Medicine2:725–734
    [Google Scholar]
  23. Laemmli U. K.. 1970; Cleavage of structural proteins during the assembly of bacteriophage T4. Nature227:680–685
    [Google Scholar]
  24. Mabbott N. A., Brown K. L., Manson J., Bruce M. E.. 1997; T-lymphocyte activation and the cellular form of the prion protein. Immunology92:161–165
    [Google Scholar]
  25. McBride P. A., Eikelenboom P., Kraal G., Fraser H., Bruce M. E.. 1992; PrP protein is associated with follicular dendritic cells of spleens and lymph nodes in uninfected and scrapie-infected mice. Journal of Pathology168:413–418
    [Google Scholar]
  26. McKinley M. P., Bolton D. C., Prusiner S. B.. 1983; A protease-resistant protein is a structural component of the scrapie prion. Cell35:57–62
    [Google Scholar]
  27. Maignien T., Lasmézas C. I., Beringue V., Dormont D., Deslys J.-P.. 1999; Pathogenesis of the oral route of infection of mice with scrapie and bovine spongiform encephalopathy agents. Journal of General Virology80:3035–3042
    [Google Scholar]
  28. Moynagh J., Schimmel H.. 1999; Tests for BSE evaluated. Bovine spongiform encephalopathies. Nature400:105
    [Google Scholar]
  29. Moynagh J., Schimmel H., Kramer G. N.. 1999; The evaluation of tests for the diagnosis of transmissible spongiform encephalopathy in bovines. In Consumer Policy and Consumer Health Protection . General directorate XXIV. Preliminary report by the European Commission. Scientific health opinions: Directorate B
    [Google Scholar]
  30. Pammer J., Weninger W., Tschachler E.. 1998; Human keratinocytes express cellular prion-related protein in vitro and during inflammatory skin diseases. American Journal of Pathology153:1353–1358
    [Google Scholar]
  31. Pammer J., Suchy A., Rendl M., Tschachler E.. 1999; Cellular prion protein expressed by bovine squamous epithelia of skin and upper gastrointestinal tract. Lancet354:1702–1703
    [Google Scholar]
  32. Prusiner S. B.. 1998; Prions. Proceeding of the National Academy of Sciences. USA95:13363–13383
    [Google Scholar]
  33. Prusiner S. B., Groth D., Serban A., Koehler R., Foster D., Torchia M., Burton D., Yang S. L., DeArmond S. J.. 1993; Ablation of the prion protein (PrP) gene in mice prevents scrapie and facilitates production of anti-PrP antibodies. Proceedings of the National Academy of Sciences, USA90:10608–10612
    [Google Scholar]
  34. Race R., Jenny A., Sutton D.. 1998; Scrapie infectivity and proteinase K-resistant prion protein in sheep placenta, brain, spleen, and lymph node: implications for transmission and antemortem diagnosis. Journal of Infectious Diseases178:949–953
    [Google Scholar]
  35. Rezaei H., Marc D., Choiset Y., Takahashi M., Hui Bon Hoa G., Haertlé T., Grosclaude J., Debey P.. 2000; High yield purification and physico–chemical properties of full-length recombinant allelic variants of sheep prion protein linked to scrapie susceptibility. European Journal of Biochemistry267:2833–2839
    [Google Scholar]
  36. Rodolfo K., Turbica I., Frobert Y., Créminon C., Fretier P., Demart S., Comoy E., Di Giamberardino L., Rezaei H., Hunsmann G., Deslys J.-P., Grassi J.. 2001; Quantitative measurement of mammalian cellular prion protein with two-site immunometric assays using specific monoclonal antibodies. Journal of Immunological Methods (in press)
    [Google Scholar]
  37. Schreuder B. E. C., van Keulen L. J. M., Vromans M. E. W., Langeveld J. P. M., Smits M. A.. 1996; Preclinical test for prion diseases. Nature381:536
    [Google Scholar]
  38. Schreuder B. E. C., van Keulen L. J. M., Vromans M. E. W., Langeveld J. P. M., Smits M.. 1998; Tonsillar biopsy and PrPSc detection in the preclinical diagnosis of scrapie. Veterinary Records142:564–568
    [Google Scholar]
  39. Shaked Y., Rosenmann H., Talmor G., Gabizon R.. 1999; A C-terminal-truncated PrP isoform is present in mature sperm. Journal of Biological Chemistry274:32153–32158
    [Google Scholar]
  40. Somerville R. A.. 1999; Host and transmissible spongiform encephalopathy agent strain control glycosylation of PrP. Journal of General Virology80:1865–1872
    [Google Scholar]
  41. van Keulen L. J. M., Schreuder B. E. C., Meloen R. H., Mooij-Harkes G., Vromans M. E. W., Langeveld J. P.. 1996; Immunohistochemical detection of prion protein in lymphoid tissues of sheep with natural scrapie. Journal of Clinical Microbiology34:1228–1231
    [Google Scholar]
  42. van Keulen L. J. M., Schreuder B. E. C., Vromans M. E. W., Langeveld J. P., Smits M. A.. 1999; Scrapie-associated prion protein in the gastrointestinal tract of sheep with natural scrapie. Journal of Comparative Pathology121:55–63
    [Google Scholar]
  43. Weissmann C.. 1996; Molecular biology of transmissible spongiform encephalopathies. FEBS Letters389:3–11
    [Google Scholar]
  44. Westaway D., DeArmond S. J., Cayetano-Canlas J., Groth D., Foster D., Yang S.-L., Torchia M., Carlson G. A., Prusiner S. B.. 1994; Degeneration of skeletal muscle, peripheral nerves, and the central nervous system in transgenic mice overexpressing wild-type prion protein. Cell76:117–129
    [Google Scholar]
http://instance.metastore.ingenta.com/content/journal/jgv/10.1099/0022-1317-82-8-2017
Loading
/content/journal/jgv/10.1099/0022-1317-82-8-2017
Loading

Data & Media loading...

Most cited this month Most Cited RSS feed

This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error