1887

Abstract

The cellular prion protein (PrP), a membrane glycoprotein anchored to the outer surface of neurons, lymphocytes and other cells, is associated directly with the pathogenesis of the transmissible spongiform encephalopathies (TSEs) occurring mainly in humans, cattle, sheep and goats. Although mice lacking PrP develop and reproduce normally and are resistant to scrapie infection, large animals lacking PrP, especially those species in which TSE occurs naturally, are currently not available. Here, five live goats cloned by gene targeting are reported. Detailed RNA-transcription and protein-expression analysis of one goat showed that one allele of the caprine gene had been disrupted functionally. No gross abnormal development or behaviour could be seen in these goats up to at least 3 months of age. These heterozygous goats are ready to be used in producing homozygous goats in which no PrP should be expressed.

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2006-04-01
2024-03-29
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References

  1. Aguzzi A., Polymenidou M. 2004; Mammalian prion biology: one century of evolving concepts. Cell 116:313–327 [CrossRef]
    [Google Scholar]
  2. Basler K., Oesch B., Scott M., Westaway D., Wälchli M., Groth D. F., McKinley M. P., Prusiner S. B., Weissmann C. 1986; Scrapie and cellular PrP isoforms are encoded by the same chromosomal gene. Cell 46:417–428 [CrossRef]
    [Google Scholar]
  3. Billinis C., Panagiotidis C. H., Psychas V., Argyroudis S., Nicolaou A., Leontides S., Papadopoulos O., Sklaviadis T. 2002; Prion protein gene polymorphisms in natural goat scrapie. J Gen Virol 83:713–721
    [Google Scholar]
  4. Büeler H., Fischer M., Lang Y., Bluethmann H., Lipp H.-P., DeArmond S. J., Prusiner S. B., Aguet M., Weissmann C. 1992; Normal development and behaviour of mice lacking the neuronal cell-surface PrP protein. Nature 356:577–582 [CrossRef]
    [Google Scholar]
  5. Büeler H., Aguzzi A., Sailer A., Greiner R.-A., Autenried P., Aguet M., Weissmann C. 1993; Mice devoid of PrP are resistant to scrapie. Cell 73:1339–1347 [CrossRef]
    [Google Scholar]
  6. Chandler R. L. 1961; Encephalopathy in mice produced by inoculation with scrapie brain material. Lancet i:1378–1379
    [Google Scholar]
  7. Dai Y., Vaught T. D., Boone J. & 12 other authors 2002; Targeted disruption of the α 1,3-galactosyltransferase gene in cloned pigs. Nat Biotechnol 20:251–255 [CrossRef]
    [Google Scholar]
  8. Denning C., Burl S., Ainslie A. & 11 other authors 2001; Deletion of the α (1,3)galactosyl transferase ( GGTA1 ) gene and the prion protein ( PrP ) gene in sheep. Nat Biotechnol 19:559–562 [CrossRef]
    [Google Scholar]
  9. Genoud N., Behrens A., Miele G., Robay D., Heppner F. L., Freigang S., Aguzzi A. 2004; Disruption of Doppel prevents neurodegeneration in mice with extensive Prnp deletions. Proc Natl Acad Sci U S A 101:4198–4203 [CrossRef]
    [Google Scholar]
  10. Kuroiwa Y., Kasinathan P., Matsushita H., Sathiyaselan J., Sullivan E. J., Kakitani M., Tomizuka K., Ishida I., Robl J. M. 2004; Sequential targeting of the genes encoding immunoglobulin- μ and prion protein in cattle. Nat Genet 36:775–780 [CrossRef]
    [Google Scholar]
  11. Lai L., Kolber-Simonds D., Park K.-W. & 11 other authors 2002; Production of α -1,3-galactosyltransferase knockout pigs by nuclear transfer cloning. Science 295:1089–1092 [CrossRef]
    [Google Scholar]
  12. Lee I. Y., Westaway D., Smit A. F. A. & 10 other authors 1998; Complete genomic sequence and analysis of the prion protein gene region from three mammalian species. Genome Res 8:1022–1037
    [Google Scholar]
  13. Legname G., Baskakov I. V., Nguyen H.-O.-B., Riesner D., Cohen F. E., DeArmond S. J., Prusiner S. B. 2004; Synthetic mammalian prions. Science 305:673–676 [CrossRef]
    [Google Scholar]
  14. Manson J. C., Clarke A. R., Hooper M. L., Aitchison L., McConnell I., Hope J. 1994; 129/Ola mice carrying a null mutation in PrP that abolishes mRNA production are developmentally normal. Mol Neurobiol 8:121–127 [CrossRef]
    [Google Scholar]
  15. McCreath K. J., Howcroft J., Campbell K. H. S., Colman A., Schnieke A. E., Kind A. J. 2000; Production of gene-targeted sheep by nuclear transfer from cultured somatic cells. Nature 405:1066–1069 [CrossRef]
    [Google Scholar]
  16. Moore R. C., Lee I. Y., Silverman G. L. & 18 other authors 1999; Ataxia in prion protein (PrP)-deficient mice is associated with upregulation of the novel PrP-like protein doppel. J Mol Biol 292:797–817 [CrossRef]
    [Google Scholar]
  17. Prusiner S. B. 1982; Novel proteinaceous infectious particles cause scrapie. Science 216:136–144 [CrossRef]
    [Google Scholar]
  18. Prusiner S. B. 1998; Prions. Proc Natl Acad Sci U S A 95:13363–13383 [CrossRef]
    [Google Scholar]
  19. 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. Proc Natl Acad Sci U S A 90:10608–10612 [CrossRef]
    [Google Scholar]
  20. Rossi D., Cozzio A., Flechsig E., Klein M. A., Rülicke T., Aguzzi A., Weissmann C. 2001; Onset of ataxia and Purkinje cell loss in PrP null mice inversely correlated with Dpl level in brain. EMBO J 20:694–702 [CrossRef]
    [Google Scholar]
  21. Sakaguchi S., Katamine S., Nishida N. & 11 other authors 1996; Loss of cerebellar Purkinje cells in aged mice homozygous for a disrupted PrP gene. Nature 380:528–531 [CrossRef]
    [Google Scholar]
  22. Schnieke A. E., Kind A. J., Ritchie W. A., Mycock K., Scott A. R., Ritchie M., Wilmut I., Colman A., Campbell K. H. S. 1997; Human factor IX transgenic sheep produced by transfer of nuclei from transfected fetal fibroblasts. Science 278:2130–2133 [CrossRef]
    [Google Scholar]
  23. Sedivy J. M., Dutriaux A. 1999; Gene targeting and somatic cell genetics: a rebirth or a coming of age?. Trends Genet 15:88–90 [CrossRef]
    [Google Scholar]
  24. Sedivy J. M., Vogelstein B., Liber H. L., Hendrickson E. A., Rosmarin A. 1999; Gene targeting in human cells without isogenic DNA. Science 283:9
    [Google Scholar]
  25. Zou X., Wang Y., Cheng Y. & 7 other authors 2002; Generation of cloned goats ( Capra hircus ) from transfected foetal fibroblast cells, the effect of donor cell cycle. Mol Reprod Dev 61:164–172 [CrossRef]
    [Google Scholar]
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