Genes contributing to prion pathogenesis.

@article{citeulike:2909255, abstract = {Prion diseases are caused by conversion of a normally folded, non-pathogenic isoform of the prion protein (PrP(C)) to a misfolded, pathogenic isoform (PrP(Sc)). Prion inoculation experiments in mice expressing homologous PrP(C) molecules on different genetic backgrounds displayed different incubation times, indicating that the conversion reaction may be influenced by other gene products. To identify genes that contribute to prion pathogenesis, we analysed incubation times of prions in mice in which the gene product was inactivated, knocked out or overexpressed. We tested 20 candidate genes, because their products either colocalize with PrP, are associated with Alzheimer's disease, are elevated during prion disease, or function in PrP-mediated signalling, PrP glycosylation, or protein maintenance. Whereas some of the candidates tested may have a role in the normal function of PrP(C), our data show that many genes previously implicated in prion replication have no discernible effect on the pathogenesis of prion disease. While most genes tested did not significantly affect survival times, ablation of the amyloid beta (A4) precursor protein (App) or interleukin-1 receptor, type I (Il1r1), and transgenic overexpression of human superoxide dismutase 1 (SOD1) prolonged incubation times by 13, 16 and 19 \%, respectively.}, address = {Institute for Neurodegenerative Diseases, University of California, San Francisco, CA, USA.}, author = {Tamg\"{u}ney, G. and Giles, K. and Glidden, D. V. and Lessard, P. and Wille, H. and Tremblay, P. and Groth, D. F. and Yehiely, F. and Korth, C. and Moore, R. C. and Tatzelt, J. and Rubinstein, E. and Boucheix, C. and Yang, X. and Stanley, P. and Lisanti, M. P. and Dwek, R. A. and Rudd, P. M. and Moskovitz, J. and Epstein, C. J. and Cruz, T. D. and Kuziel, W. A. and Maeda, N. and Sap, J. and Ashe, K. H. and Carlson, G. A. and Tesseur, I. and Wyss-Coray, T. and Mucke, L. and Weisgraber, K. H. and Mahley, R. W. and Cohen, F. E. and Prusiner, S. B. }, citeulike-article-id = {2909255}, issn = {0022-1317}, journal = {The Journal of general virology}, keywords = {genetics, prion\_diseases}, month = {July}, number = {Pt 7}, pages = {1777--1788}, posted-at = {2008-06-20 02:28:20}, priority = {5}, title = {Genes contributing to prion pathogenesis.}, url = {http://view.ncbi.nlm.nih.gov/pubmed/18559949}, volume = {89}, year = {2008} }

TY - JOUR ID - citeulike:2909255 L3 - citeulike-article-id:2909255 TI - Genes contributing to prion pathogenesis. JF - The Journal of general virology VL - 89 IS - Pt 7 SP - 1777 EP - 1788 AD - Institute for Neurodegenerative Diseases, University of California, San Francisco, CA, USA. SN - 0022-1317 N2 - Prion diseases are caused by conversion of a normally folded, non-pathogenic isoform of the prion protein (PrP(C)) to a misfolded, pathogenic isoform (PrP(Sc)). Prion inoculation experiments in mice expressing homologous PrP(C) molecules on different genetic backgrounds displayed different incubation times, indicating that the conversion reaction may be influenced by other gene products. To identify genes that contribute to prion pathogenesis, we analysed incubation times of prions in mice in which the gene product was inactivated, knocked out or overexpressed. We tested 20 candidate genes, because their products either colocalize with PrP, are associated with Alzheimer's disease, are elevated during prion disease, or function in PrP-mediated signalling, PrP glycosylation, or protein maintenance. Whereas some of the candidates tested may have a role in the normal function of PrP(C), our data show that many genes previously implicated in prion replication have no discernible effect on the pathogenesis of prion disease. While most genes tested did not significantly affect survival times, ablation of the amyloid beta (A4) precursor protein (App) or interleukin-1 receptor, type I (Il1r1), and transgenic overexpression of human superoxide dismutase 1 (SOD1) prolonged incubation times by 13, 16 and 19 %, respectively. KW - genetics KW - prion_diseases AU - Tamgüney, G AU - Giles, K AU - Glidden, DV AU - Lessard, P AU - Wille, H AU - Tremblay, P AU - Groth, DF AU - Yehiely, F AU - Korth, C AU - Moore, RC AU - Tatzelt, J AU - Rubinstein, E AU - Boucheix, C AU - Yang, X AU - Stanley, P AU - Lisanti, MP AU - Dwek, RA AU - Rudd, PM AU - Moskovitz, J AU - Epstein, CJ AU - Cruz, TD AU - Kuziel, WA AU - Maeda, N AU - Sap, J AU - Ashe, KH AU - Carlson, GA AU - Tesseur, I AU - Wyss-Coray, T AU - Mucke, L AU - Weisgraber, KH AU - Mahley, RW AU - Cohen, FE AU - Prusiner, SB PY - 2008/07// UR - http://view.ncbi.nlm.nih.gov/pubmed/18559949 ER -