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

Prnp  -  prion protein

Mus musculus

Synonyms: AA960666, AI325101, CD230, Major prion protein, PrP, ...
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 Prnp


Psychiatry related information on Prnp


High impact information on Prnp


Chemical compound and disease context of Prnp

  • Mild formaldehyde crosslinking of mouse neuroblastoma cells (N2a) that are susceptible to prion infection revealed the presence of PrP(C) in high molecular mass (HMM) protein complexes of 200 to 225 kDa [15].
  • Overexpression of PrPC by injection of rAd (replication-defective recombinant adenoviral)-PGK (phosphoglycerate kinase)-PrPC-Flag into ischemic rat brain improved neurological behavior and reduced the volume of cerebral infarction, which is supportive of a role for PrPC in the neuroprotective adaptive cellular response to ischemic lesions [16].
  • Neither detergent (2% Sarkosyl) extraction nor limited proteinase K digestion of scrapie microsomes produced recognizable prion amyloid rods [17].
  • More strikingly, cellular MTT formazan exocytosis revealed the formation of bioactive amyloid species in prion-infected mouse N2a neuroblastoma cells [18].
  • We used wild-type mice, PrP knockout (Prnp(-/-)) animals and transgenic mice that lack the octarepeat region (C4/-) and subjected them to controlled ischemia [19].

Biological context of Prnp

  • The interaction between the Prnp and Prnd genes in mouse cerebellar neurons may have a physical correlate in competition between Dpl and PrP(C) within a common biochemical pathway that when mis-regulated leads to apoptosis [20].
  • Remarkably, Dpl-programmed ataxia is rescued by wild-type Prnp transgenes [20].
  • However, little is known about the cell death of Prnp(-/-) neuronal cells under serum deprivation [21].
  • We conclude that the new allele, Prnp(c), modulates incubation time but not neuropathology and that the previous classification of mice into two distinct groups based on incubation time and Prnp genotype should now be revised [22].
  • 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 [23].

Anatomical context of Prnp


Associations of Prnp with chemical compounds

  • Mice lacking the cellular prion protein (PrP(c)) gene (Prnp) present a decreased astrocytic glutamate uptake in cultures, higher neuronal excitability in vitro and sensitivity to pro-convulsant drugs in vivo, and age-dependent memory impairment [26].
  • A common human prion-protein-gene (PRNP) polymorphism (encoding either methionine or valine at codon 129) is a strong susceptibility factor for sporadic and acquired prion disease [4].
  • 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 [27].
  • In addition, Ca(2+) levels of mitochondria were increased, whereas mitochondrial membrane potentials were decreased in PrP(-/-) cells [28].
  • Combined, ultrastructural and thioflavin assays, together with microglial cytokine release measurements, provide a test system to screen potential, fibrillarity impeding therapeutics for prion disease [29].
  • Mutations within PrP 98-110, substituting all 4 wild-type lysine residues with alanine residues, prevented conversion to PrP(Sc) [30].

Physical interactions of Prnp

  • We established the linkage relationship between the prion gene complex (Prn) and other chromosome 2 genes; the gene order, proximal to distal, is B2m-II-1a-Prn-Itp-A [31].
  • Additionally, similar levels of PrP/N-CAM complexes were found in N2a and prion-infected N2a (ScN2a) cells [15].
  • In this configuration, C1q bound avidly to PrP, with a K(D) of 5.4 nM (k(on) = 2.4 x 10(5) M(-1) s(-1); k(off) = 1.3 x 10(-3) s(-1)) [32].
  • The cellular prion protein (PrP) selectively binds to Bcl-2 in the yeast two-hybrid system [33].
  • Expression of prion protein increases cellular copper binding and antioxidant enzyme activities but not copper delivery [34].

Co-localisations of Prnp


Regulatory relationships of Prnp


Other interactions of Prnp

  • Prion protein recruits its neuronal receptor NCAM to lipid rafts to activate p59fyn and to enhance neurite outgrowth [41].
  • 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 [42].
  • These phenomena, together with the founder effect, would favor apparent linkage disequilibrium between Prn-p and Prn-i. Therefore, transmission genetics may underestimate the number of genes in Prn [31].
  • Recombination suppression in the B2m-Prn-p interval occurred during the crosses involved in transferring the I/LnJ Prnb complex into a C57BL/6J background [31].
  • Probing the conformation of the prion protein within a single amyloid fibril using a novel immunoconformational assay [43].

Analytical, diagnostic and therapeutic context of Prnp


  1. Prions prevent brain damage after experimental brain injury: a preliminary report. Hoshino, S., Inoue, K., Yokoyama, T., Kobayashi, S., Asakura, T., Teramoto, A., Itohara, S. Acta Neurochir. Suppl. (2003) [Pubmed]
  2. Astrocyte-specific expression of hamster prion protein (PrP) renders PrP knockout mice susceptible to hamster scrapie. Raeber, A.J., Race, R.E., Brandner, S., Priola, S.A., Sailer, A., Bessen, R.A., Mucke, L., Manson, J., Aguzzi, A., Oldstone, M.B., Weissmann, C., Chesebro, B. EMBO J. (1997) [Pubmed]
  3. 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]
  4. Sporadic--but not variant--Creutzfeldt-Jakob disease is associated with polymorphisms upstream of PRNP exon 1. Mead, S., Mahal, S.P., Beck, J., Campbell, T., Farrall, M., Fisher, E., Collinge, J. Am. J. Hum. Genet. (2001) [Pubmed]
  5. Inducible overexpression of wild-type prion protein in the muscles leads to a primary myopathy in transgenic mice. Huang, S., Liang, J., Zheng, M., Li, X., Wang, M., Wang, P., Vanegas, D., Wu, D., Chakraborty, B., Hays, A.P., Chen, K., Chen, S.G., Booth, S., Cohen, M., Gambetti, P., Kong, Q. Proc. Natl. Acad. Sci. U.S.A. (2007) [Pubmed]
  6. Accumulation of prion protein in the brain that is not associated with transmissible disease. Piccardo, P., Manson, J.C., King, D., Ghetti, B., Barron, R.M. Proc. Natl. Acad. Sci. U.S.A. (2007) [Pubmed]
  7. Lymph nodal prion replication and neuroinvasion in mice devoid of follicular dendritic cells. Prinz, M., Montrasio, F., Klein, M.A., Schwarz, P., Priller, J., Odermatt, B., Pfeffer, K., Aguzzi, A. Proc. Natl. Acad. Sci. U.S.A. (2002) [Pubmed]
  8. Immunohistochemical detection of apolipoprotein E within prion-associated lesions in squirrel monkey brains. Nakamura, S., Ono, F., Hamano, M., Odagiri, K., Kubo, M., Komatsuzaki, K., Terao, K., Shinagawa, M., Takahashi, K., Yoshikawa, Y. Acta Neuropathol. (2000) [Pubmed]
  9. Bax deletion prevents neuronal loss but not neurological symptoms in a transgenic model of inherited prion disease. Chiesa, R., Piccardo, P., Dossena, S., Nowoslawski, L., Roth, K.A., Ghetti, B., Harris, D.A. Proc. Natl. Acad. Sci. U.S.A. (2005) [Pubmed]
  10. Sleep and sleep regulation in normal and prion protein-deficient mice. Tobler, I., Deboer, T., Fischer, M. J. Neurosci. (1997) [Pubmed]
  11. Glycosylation deficiency at either one of the two glycan attachment sites of cellular prion protein preserves susceptibility to bovine spongiform encephalopathy and scrapie infections. Neuendorf, E., Weber, A., Saalmueller, A., Schatzl, H., Reifenberg, K., Pfaff, E., Groschup, M.H. J. Biol. Chem. (2004) [Pubmed]
  12. Mice with gene targetted prion protein alterations show that Prnp, Sinc and Prni are congruent. Moore, R.C., Hope, J., McBride, P.A., McConnell, I., Selfridge, J., Melton, D.W., Manson, J.C. Nat. Genet. (1998) [Pubmed]
  13. Expression of amino-terminally truncated PrP in the mouse leading to ataxia and specific cerebellar lesions. Shmerling, D., Hegyi, I., Fischer, M., Blättler, T., Brandner, S., Götz, J., Rülicke, T., Flechsig, E., Cozzio, A., von Mering, C., Hangartner, C., Aguzzi, A., Weissmann, C. Cell (1998) [Pubmed]
  14. Rescue of neurophysiological phenotype seen in PrP null mice by transgene encoding human prion protein. Whittington, M.A., Sidle, K.C., Gowland, I., Meads, J., Hill, A.F., Palmer, M.S., Jefferys, J.G., Collinge, J. Nat. Genet. (1995) [Pubmed]
  15. Binding of neural cell adhesion molecules (N-CAMs) to the cellular prion protein. Schmitt-Ulms, G., Legname, G., Baldwin, M.A., Ball, H.L., Bradon, N., Bosque, P.J., Crossin, K.L., Edelman, G.M., DeArmond, S.J., Cohen, F.E., Prusiner, S.B. J. Mol. Biol. (2001) [Pubmed]
  16. Overexpression of PrPC by adenovirus-mediated gene targeting reduces ischemic injury in a stroke rat model. Shyu, W.C., Lin, S.Z., Chiang, M.F., Ding, D.C., Li, K.W., Chen, S.F., Yang, H.I., Li, H. J. Neurosci. (2005) [Pubmed]
  17. Scrapie prion rod formation in vitro requires both detergent extraction and limited proteolysis. McKinley, M.P., Meyer, R.K., Kenaga, L., Rahbar, F., Cotter, R., Serban, A., Prusiner, S.B. J. Virol. (1991) [Pubmed]
  18. The formation of bioactive amyloid species by prion proteins in vitro and in cells. Liu, Y., Ritter, C., Riek, R., Schubert, D. Neurosci. Lett. (2006) [Pubmed]
  19. The role of the octarepeat region in neuroprotective function of the cellular prion protein. Mitteregger, G., Vosko, M., Krebs, B., Xiang, W., Kohlmannsperger, V., Nölting, S., Hamann, G.F., Kretzschmar, H.A. Brain Pathol. (2007) [Pubmed]
  20. The prion gene complex encoding PrP(C) and Doppel: insights from mutational analysis. Mastrangelo, P., Westaway, D. Gene (2001) [Pubmed]
  21. Tumor necrosis factor attenuates prion protein-deficient neuronal cell death by increases in anti-apoptotic Bcl-2 family proteins. Sakudo, A., Lee, D.C., Saeki, K., Matsumoto, Y., Itohara, S., Onodera, T. Biochem. Biophys. Res. Commun. (2003) [Pubmed]
  22. Identification and characterization of a novel mouse prion gene allele. Lloyd, S.E., Thompson, S.R., Beck, J.A., Linehan, J.M., Wadsworth, J.D., Brandner, S., Collinge, J., Fisher, E.M. Mamm. Genome (2004) [Pubmed]
  23. 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]
  24. A mouse prion protein transgene rescues mice deficient for the prion protein gene from purkinje cell degeneration and demyelination. Nishida, N., Tremblay, P., Sugimoto, T., Shigematsu, K., Shirabe, S., Petromilli, C., Erpel, S.P., Nakaoke, R., Atarashi, R., Houtani, T., Torchia, M., Sakaguchi, S., DeArmond, S.J., Prusiner, S.B., Katamine, S. Lab. Invest. (1999) [Pubmed]
  25. Expression of Prnp mRNA (prion protein gene) in mouse spermatogenic cells. Fujisawa, M., Kanai, Y., Nam, S.Y., Maeda, S., Nakamuta, N., Kano, K., Kurohmaru, M., Hayashi, Y. J. Reprod. Dev. (2004) [Pubmed]
  26. Synaptosomal glutamate release and uptake in mice lacking the cellular prion protein. Thais, M.E., Carqueja, C.L., Santos, T.G., Silva, R.V., Stroeh, E., Machado, R.S., Wahlheim, D.O., Bianchin, M.M., Sakamoto, A.C., Brentani, R.R., Martins, V.R., Walz, R., Tasca, C.I. Brain Res. (2006) [Pubmed]
  27. 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]
  28. The cellular prion protein (PrPC) prevents apoptotic neuronal cell death and mitochondrial dysfunction induced by serum deprivation. Kim, B.H., Lee, H.G., Choi, J.K., Kim, J.I., Choi, E.K., Carp, R.I., Kim, Y.S. Brain Res. Mol. Brain Res. (2004) [Pubmed]
  29. Activation of human microglia by fibrillar prion protein-related peptides is enhanced by amyloid-associated factors SAP and C1q. Veerhuis, R., Boshuizen, R.S., Morbin, M., Mazzoleni, G., Hoozemans, J.J., Langedijk, J.P., Tagliavini, F., Langeveld, J.P., Eikelenboom, P. Neurobiol. Dis. (2005) [Pubmed]
  30. Identifying key components of the PrPC-PrPSc replicative interface. Abalos, G.C., Cruite, J.T., Bellon, A., Hemmers, S., Akagi, J., Mastrianni, J.A., Williamson, R.A., Solforosi, L. J. Biol. Chem. (2008) [Pubmed]
  31. Genetics and polymorphism of the mouse prion gene complex: control of scrapie incubation time. Carlson, G.A., Goodman, P.A., Lovett, M., Taylor, B.A., Marshall, S.T., Peterson-Torchia, M., Westaway, D., Prusiner, S.B. Mol. Cell. Biol. (1988) [Pubmed]
  32. Complement protein C1q recognizes a conformationally modified form of the prion protein. Blanquet-Grossard, F., Thielens, N.M., Vendrely, C., Jamin, M., Arlaud, G.J. Biochemistry (2005) [Pubmed]
  33. The cellular prion protein (PrP) selectively binds to Bcl-2 in the yeast two-hybrid system. Kurschner, C., Morgan, J.I. Brain Res. Mol. Brain Res. (1995) [Pubmed]
  34. Expression of prion protein increases cellular copper binding and antioxidant enzyme activities but not copper delivery. Rachidi, W., Vilette, D., Guiraud, P., Arlotto, M., Riondel, J., Laude, H., Lehmann, S., Favier, A. J. Biol. Chem. (2003) [Pubmed]
  35. The cellular prion protein colocalizes with the dystroglycan complex in the brain. Keshet, G.I., Bar-Peled, O., Yaffe, D., Nudel, U., Gabizon, R. J. Neurochem. (2000) [Pubmed]
  36. Prion replication alters the distribution of synaptophysin and caveolin 1 in neuronal lipid rafts. Russelakis-Carneiro, M., Hetz, C., Maundrell, K., Soto, C. Am. J. Pathol. (2004) [Pubmed]
  37. Prion-induced amyloid heart disease with high blood infectivity in transgenic mice. Trifilo, M.J., Yajima, T., Gu, Y., Dalton, N., Peterson, K.L., Race, R.E., Meade-White, K., Portis, J.L., Masliah, E., Knowlton, K.U., Chesebro, B., Oldstone, M.B. Science (2006) [Pubmed]
  38. Chronic lymphocytic inflammation specifies the organ tropism of prions. Heikenwalder, M., Zeller, N., Seeger, H., Prinz, M., Klöhn, P.C., Schwarz, P., Ruddle, N.H., Weissmann, C., Aguzzi, A. Science (2005) [Pubmed]
  39. NADPH oxidase and extracellular regulated kinases 1/2 are targets of prion protein signaling in neuronal and nonneuronal cells. Schneider, B., Mutel, V., Pietri, M., Ermonval, M., Mouillet-Richard, S., Kellermann, O. Proc. Natl. Acad. Sci. U.S.A. (2003) [Pubmed]
  40. Follicular dendritic cell dedifferentiation by treatment with an inhibitor of the lymphotoxin pathway dramatically reduces scrapie susceptibility. Mabbott, N.A., Young, J., McConnell, I., Bruce, M.E. J. Virol. (2003) [Pubmed]
  41. Prion protein recruits its neuronal receptor NCAM to lipid rafts to activate p59fyn and to enhance neurite outgrowth. Santuccione, A., Sytnyk, V., Leshchyns'ka, I., Schachner, M. J. Cell Biol. (2005) [Pubmed]
  42. 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]
  43. Probing the conformation of the prion protein within a single amyloid fibril using a novel immunoconformational assay. Novitskaya, V., Makarava, N., Bellon, A., Bocharova, O.V., Bronstein, I.B., Williamson, R.A., Baskakov, I.V. J. Biol. Chem. (2006) [Pubmed]
  44. Prion protein as trans-interacting partner for neurons is involved in neurite outgrowth and neuronal survival. Chen, S., Mangé, A., Dong, L., Lehmann, S., Schachner, M. Mol. Cell. Neurosci. (2003) [Pubmed]
  45. Decreased cell surface prion protein in mouse models of prion disease. Griffin, J.K., Terry, L.A., Jackman, R., Yousefi, M., Cashman, N.R. Neuroreport (2007) [Pubmed]
  46. Intracerebroventricular delivery of dominant negative prion protein in a mouse model of iatrogenic Creutzfeldt-Jakob disease after dura graft transplantation. Furuya, K., Kawahara, N., Yamakawa, Y., Kishida, H., Hachiya, N.S., Nishijima, M., Kirino, T., Kaneko, K. Neurosci. Lett. (2006) [Pubmed]
  47. Prion protein expression in mammalian lenses. Frederikse, P.H., Zigler, S.J., Farnsworth, P.N., Carper, D.A. Curr. Eye Res. (2000) [Pubmed]
WikiGenes - Universities