The world's first wiki where authorship really matters (Nature Genetics, 2008). Due credit and reputation for authors. Imagine a global collaborative knowledge base for original thoughts. Search thousands of articles and collaborate with scientists around the globe.

wikigene or wiki gene protein drug chemical gene disease author authorship tracking collaborative publishing evolutionary knowledge reputation system wiki2.0 global collaboration genes proteins drugs chemicals diseases compound
Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)



Gene Review

Prnd  -  prion protein dublet

Mus musculus

Synonyms: AI450264, Doppelganger, Dpl, PrPLP, Prion-like protein doppel, ...
Welcome! If you are familiar with the subject of this article, you can contribute to this open access knowledge base by deleting incorrect information, restructuring or completely rewriting any text. Read more.

Disease relevance of Prnd

  • Both develop normally and display an identical male sterility phenotype that differs from that reported for another Prnd(-/-) mouse line [1].
  • When Prnd-deficient neural tissue was inoculated with scrapie prions, typical features of prion pathology including spongiosis, gliosis and PrPSc accumulation, were observed [2].
  • Linked expression of Prnp and Prnd may cause several neurodegenerative disorders [3].
  • Using recombinant Dpl expressed in Escherichia coli and mouse neuroblastoma cells we demonstrate that wild type (wt) Dpl, like PrP(C), adopts a predominantly alpha-helical conformation, forms intramolecular disulfide bonds, has two N-linked oligosaccharides, and is presented on the cell surface via a glycosylphosphatidylinositol anchor [4].
  • Analysis of doppel protein toxicity [5].

High impact information on Prnd

  • In contrast to its homologue PrP(C), initial studies suggest that Dpl is dispensable for prion disease progression and for the generation of PrP(Sc) [6].
  • Dpl deficiency did not interfere with embryonic and postnatal development, but resulted in male sterility [7].
  • Dpl protein was expressed at late stages of spermiogenesis, and spermatids of Dpl mutants were reduced in numbers, immobile, malformed and unable to fertilize oocytes in vitro [7].
  • We conclude that Dpl regulates male fertility by controlling several aspects of male gametogenesis and sperm-egg interaction [7].
  • PrP(C)-deficient mice do not exhibit major pathologies, perhaps because they express a protein termed Dpl, which shares significant biochemical and structural homology with PrP(C) [7].

Biological context of Prnd

  • Removal of its ORF does not result in pathological phenotypes, but deletions extending into the upstream intron result in cerebellar degeneration, possibly because of ectopic cis-activation of the Prnd locus that encodes the PrP(C) homologue Doppel (Dpl) [8].
  • Up-regulation of Prnd mRNA in two distinct lines of PrP gene ablated (Prnp(0/0)) mice, designated Rcm0 and Ngsk, is associated with death of Purkinje cells [4].
  • The reverse transcription polymerase chain reaction revealed that serum deprivation did not increase Prnp/Prnd chimeric mRNAs, which in fact was translated into a small amount of Dpl in HpL3-4 cells, whereas serum deprivation induced apoptotic cell death of HpL3-4 cells [9].
  • These responses are suggestive of increased oxidative stress in the brains of the Dpl-expressing Prnp(0/0) mice [10].
  • Like PrP, Dpl mRNA is expressed during embryogenesis but, in contrast to PrP, it is expressed minimally in the CNS [11].

Anatomical context of Prnd

  • The Prnd gene is expressed in mouse embryos; in adult mice its transcripts are present in heart, mammary gland, spleen, testes and, in contrast to Prnp, only at very low levels in the adult CNS [12].
  • No detergent-insoluble PrPLP/Dpl was detectable in the central nervous system of Ngsk Prnp0/0 mice even after the onset of ataxia [13].
  • After in vitro differentiation and grafting into adult brains of PrPC-deficient Prnp0/0 mice, Dpl-deficient ES cell-derived grafts contained all neural lineages analyzed, including neurons and astrocytes [2].
  • CONCLUSIONS: These findings strongly suggest that ectopic PrPLP/Dpl in the absence of PrP(C) is actively involved in the glial-cell activation in the brain [14].
  • A neuronal cell line that does not express either prion or doppel proteins [15].

Associations of Prnd with chemical compounds

  • A cell model which was previously established from Rikn mice (PrP-/-) remains problematic because of its ectopic expression of the doppel (Dpl) which may have a neurotoxic effect [15].
  • Using Triton X-114 phase partitioning to enrich for glycosylphosphatidylinositol-anchored proteins, Dpl was detected in brain samples from Rcm0 Prnp(0/0) mice but was absent in equivalent samples from wt mice and ZrchI Prnp(0/0) mice, indicating that ectopic expression of this protein may cause cerebellar pathology in Rcm0 mice [4].
  • Only partial unfolding of doppel or the mutant occurs at elevated temperature, but both exhibit full and reversible unfolding in chemical denaturation with urea [16].

Physical interactions of Prnd

  • The activation capacity of the related USF-2, c-Myc and HIF-2alpha proteins was lower compared to USF-1 suggesting that USF-1 is the major E-box-binding transcription factor regulating the Prnd promoter [17].

Regulatory relationships of Prnd

  • Dpl is expressed in the brains of mice that do not express PrP, and Dpl is known to be toxic to neurons [18].
  • Using immunoblot analyses, we further demonstrate that doppel expression activates caspase-10 as well as caspase-3, but does not activate caspase-9 [19].

Other interactions of Prnd

  • These findings raise the possibility that the cells of the molecular layer express an auxiliary protein, provisionally designated protein X, which is involved in prion formation and is likely to be distinct from the protein that mediates Dpl-induced degeneration [20].
  • Involvement of upstream stimulatory factor in regulation of the mouse Prnd gene coding for Doppel protein [17].
  • In contrast, Tg(Dpl)ZrchI mice showed cerebellar granule and Purkinje cell loss; the age of onset of ataxia was inversely proportional to the levels of Dpl protein [21].
  • To evaluate whether the two proteins caused cerebellar neurodegeneration by the same mechanism, we generated transgenic mice selectively expressing Dpl in Purkinje cells by the same L7 promoter [22].
  • Lymphocytes incubated for 18 h with IL-2 and with IFNgamma overexpressed Dpl [23].

Analytical, diagnostic and therapeutic context of Prnd


  1. Male infertility and DNA damage in Doppel knockout and prion protein/Doppel double-knockout mice. Paisley, D., Banks, S., Selfridge, J., McLennan, N.F., Ritchie, A.M., McEwan, C., Irvine, D.S., Saunders, P.T., Manson, J.C., Melton, D.W. Am. J. Pathol. (2004) [Pubmed]
  2. Normal neurogenesis and scrapie pathogenesis in neural grafts lacking the prion protein homologue Doppel. Behrens, A., Brandner, S., Genoud, N., Aguzzi, A. EMBO Rep. (2001) [Pubmed]
  3. Japanese scrapie cases. Onodera, T., Saeki, K. Jpn. J. Infect. Dis. (2000) [Pubmed]
  4. Doppel is an N-glycosylated, glycosylphosphatidylinositol-anchored protein. Expression in testis and ectopic production in the brains of Prnp(0/0) mice predisposed to Purkinje cell loss. Silverman, G.L., Qin, K., Moore, R.C., Yang, Y., Mastrangelo, P., Tremblay, P., Prusiner, S.B., Cohen, F.E., Westaway, D. J. Biol. Chem. (2000) [Pubmed]
  5. Analysis of doppel protein toxicity. Cui, T., Holme, A., Sassoon, J., Brown, D.R. Mol. Cell. Neurosci. (2003) [Pubmed]
  6. Small is not beautiful: antagonizing functions for the prion protein PrP(C) and its homologue Dpl. Behrens, A., Aguzzi, A. Trends Neurosci. (2002) [Pubmed]
  7. Absence of the prion protein homologue Doppel causes male sterility. Behrens, A., Genoud, N., Naumann, H., Rülicke, T., Janett, F., Heppner, F.L., Ledermann, B., Aguzzi, A. EMBO J. (2002) [Pubmed]
  8. Disruption of Doppel prevents neurodegeneration in mice with extensive Prnp deletions. Genoud, N., Behrens, A., Miele, G., Robay, D., Heppner, F.L., Freigang, S., Aguzzi, A. Proc. Natl. Acad. Sci. U.S.A. (2004) [Pubmed]
  9. Cell-autonomous PrP-Doppel interaction regulates apoptosis in PrP gene-deficient neuronal cells. Sakudo, A., Lee, D.C., Nakamura, I., Taniuchi, Y., Saeki, K., Matsumoto, Y., Itohara, S., Ikuta, K., Onodera, T. Biochem. Biophys. Res. Commun. (2005) [Pubmed]
  10. Induction of HO-1 and NOS in doppel-expressing mice devoid of PrP: implications for doppel function. Wong, B.S., Liu, T., Paisley, D., Li, R., Pan, T., Chen, S.G., Perry, G., Petersen, R.B., Smith, M.A., Melton, D.W., Gambetti, P., Brown, D.R., Sy, M.S. Mol. Cell. Neurosci. (2001) [Pubmed]
  11. Ataxia in prion protein (PrP)-deficient mice is associated with upregulation of the novel PrP-like protein doppel. Moore, R.C., Lee, I.Y., Silverman, G.L., Harrison, P.M., Strome, R., Heinrich, C., Karunaratne, A., Pasternak, S.H., Chishti, M.A., Liang, Y., Mastrangelo, P., Wang, K., Smit, A.F., Katamine, S., Carlson, G.A., Cohen, F.E., Prusiner, S.B., Melton, D.W., Tremblay, P., Hood, L.E., Westaway, D. J. Mol. Biol. (1999) [Pubmed]
  12. Doppel: the prion's double. Golańiska, E., Flirski, M., Liberski, P.P. Folia neuropathologica / Association of Polish Neuropathologists and Medical Research Centre, Polish Academy of Sciences. (2004) [Pubmed]
  13. Deletion of N-terminal residues 23-88 from prion protein (PrP) abrogates the potential to rescue PrP-deficient mice from PrP-like protein/doppel-induced Neurodegeneration. Atarashi, R., Nishida, N., Shigematsu, K., Goto, S., Kondo, T., Sakaguchi, S., Katamine, S. J. Biol. Chem. (2003) [Pubmed]
  14. Abnormal activation of glial cells in the brains of prion protein-deficient mice ectopically expressing prion protein-like protein, PrPLP/Dpl. Atarashi, R., Sakaguchi, S., Shigematsu, K., Arima, K., Okimura, N., Yamaguchi, N., Li, A., Kopacek, J., Katamine, S. Mol. Med. (2001) [Pubmed]
  15. A neuronal cell line that does not express either prion or doppel proteins. Kim, B.H., Kim, J.I., Choi, E.K., Carp, R.I., Kim, Y.S. Neuroreport (2005) [Pubmed]
  16. Stability and conformational properties of doppel, a prion-like protein, and its single-disulphide mutant. Whyte, S.M., Sylvester, I.D., Martin, S.R., Gill, A.C., Wopfner, F., Schätzl, H.M., Dodson, G.G., Bayley, P.M. Biochem. J. (2003) [Pubmed]
  17. Involvement of upstream stimulatory factor in regulation of the mouse Prnd gene coding for Doppel protein. Sepelakova, J., Takacova, M., Pastorekova, S., Kopacek, J. Biochim. Biophys. Acta (2005) [Pubmed]
  18. NMR solution structure of the peptide fragment 1-30, derived from unprocessed mouse Doppel protein, in DHPC micelles. Papadopoulos, E., Oglecka, K., Mäler, L., Jarvet, J., Wright, P.E., Dyson, H.J., Gräslund, A. Biochemistry (2006) [Pubmed]
  19. Doppel-induced apoptosis and counteraction by cellular prion protein in neuroblastoma and astrocytes. Qin, K., Zhao, L., Tang, Y., Bhatta, S., Simard, J.M., Zhao, R.Y. Neuroscience (2006) [Pubmed]
  20. Prion and doppel proteins bind to granule cells of the cerebellum. Legname, G., Nelken, P., Guan, Z., Kanyo, Z.F., DeArmond, S.J., Prusiner, S.B. Proc. Natl. Acad. Sci. U.S.A. (2002) [Pubmed]
  21. Doppel-induced cerebellar degeneration in transgenic mice. Moore, R.C., Mastrangelo, P., Bouzamondo, E., Heinrich, C., Legname, G., Prusiner, S.B., Hood, L., Westaway, D., DeArmond, S.J., Tremblay, P. Proc. Natl. Acad. Sci. U.S.A. (2001) [Pubmed]
  22. Transgene-driven expression of the Doppel protein in Purkinje cells causes Purkinje cell degeneration and motor impairment. Anderson, L., Rossi, D., Linehan, J., Brandner, S., Weissmann, C. Proc. Natl. Acad. Sci. U.S.A. (2004) [Pubmed]
  23. Bovine prion (PrP) and Doppel (Dpl) proteins expression after in vitro leukocyte activation or Dpl/PrP blocking. Paltrinieri, S., Spagnolo, V., Giordano, A., Gelmetti, D., Comazzi, S. J. Cell. Physiol. (2006) [Pubmed]
  24. Genetic mapping of activity determinants within cellular prion proteins: N-terminal modules in PrPC offset pro-apoptotic activity of the Doppel helix B/B' region. Drisaldi, B., Coomaraswamy, J., Mastrangelo, P., Strome, B., Yang, J., Watts, J.C., Chishti, M.A., Marvi, M., Windl, O., Ahrens, R., Major, F., Sy, M.S., Kretzschmar, H., Fraser, P.E., Mount, H.T., Westaway, D. J. Biol. Chem. (2004) [Pubmed]
  25. Physiological expression of the gene for PrP-like protein, PrPLP/Dpl, by brain endothelial cells and its ectopic expression in neurons of PrP-deficient mice ataxic due to Purkinje cell degeneration. Li, A., Sakaguchi, S., Shigematsu, K., Atarashi, R., Roy, B.C., Nakaoke, R., Arima, K., Okimura, N., Kopacek, J., Katamine, S. Am. J. Pathol. (2000) [Pubmed]
  26. The PrP-like protein Doppel binds copper. Qin, K., Coomaraswamy, J., Mastrangelo, P., Yang, Y., Lugowski, S., Petromilli, C., Prusiner, S.B., Fraser, P.E., Goldberg, J.M., Chakrabartty, A., Westaway, D. J. Biol. Chem. (2003) [Pubmed]
  27. Sequence determination and expression of the ovine doppel-encoding gene in transgenic mice. Essalmani, R., Taourit, S., Besnard, N., Vilotte, J.L. Gene (2002) [Pubmed]
  28. The PrP-like protein Doppel gene in sheep and cattle: cDNA sequence and expression. Tranulis, M.A., Espenes, A., Comincini, S., Skretting, G., Harbitz, I. Mamm. Genome (2001) [Pubmed]
WikiGenes - Universities